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 Textbook of
Clinical Embryology

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 Textbook of
Clinical Embryology
Second Edition

Vishram Singh, mbbs, ms, phd(hc), micps, fasi, fimsa

Professor and Head, Department of Anatomy
Santosh Medical College
Member Academic Council and Core Committee, PhD Course
Santosh University, Ghaziabad, NCR, Delhi

Editor-in-chief, Journal of the Anatomical Society of India

Examiner in National and International Universities; Member, Editorial Board
Indian Journal of Otology; Journal of Anatomy and Cell Biology
Ex-Vice President, Anatomical Society of India
Medicolegal Advisor, ICPS, India
Consulting Editor, ABI, North Carolina, USA
Associate Editor, Acta Medica International
Member, COPE (England & Wales)

Formerly at: GSVM Medical College, Kanpur

King George’s Medical College, Lucknow
Al-Arab Medical University, Benghazi (Libya)
All India Institute of Medical Sciences, New Delhi

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Textbook of Clinical Embryology, 2nd Edition, Vishram Singh

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 Dedicated to
My Parents
Late Smt Ganga Devi Singh
and
Late Shri HR Singh an ever guiding force in my life

My Wife
Late Smt Manorama Rani Singh for her unending support and
cooperation of my pursuits

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 Preface to the Second Edition

It gives me great pleasure to present second edition of Textbook of Clinical Embryology, which is widely used not only by the
undergraduate students but also by the postgraduate students of anatomy, pediatrics, and obstetrics and gynecology. The
popularity of this book reflects the appeal of its concept building approach and easy to understand language. This approach
has also been retained in this edition with unique problem-solving approach and its utility in highlighting the embryo-
logical basis of clinical problems. Based on a large number of suggestions, criticisms and comments received from the
VS-Chapter-06.indd 71 6/21/2012 3:50:09 PM

students and fellow academicians, the text has been extensively revised for further improvement of the book.
In this edition new features such as learning objectives, facts to remember, new line diagrams, tables, and flowcharts have
been included to further enhance the utility of this book. In addition, at the end of each chapter the summary of timing of
events is given for easy recall. Most of the diagrams are completely revised and redrawn for easy understanding and repro-
ducibility in the exam by the students. The topics on fertilization, gametogenesis, extraembryonic membranes, heart and
blood vessels, urogenital system and sensory organs have been thoroughly revised in detail due to high incidence of con-
genital problems associated with these systems.
In addition, complimentary access to online animations, chapter-wise image bank along with complete e-book is also pro-
vided.
I sincerely hope that the readers will find this edition more interesting and useful than the previous one. I would love to
get fair comments, good or bad, both from students and teachers.
“Providing good teaching material or its source and inspiring the students for learning is the real contribution of a teacher.”

Vishram Singh

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 Preface to the First Edition

Textbook of Clinical Embryology has been carefully planned for the first year medical and dental students. It follows the revised
anatomy curriculum of the Medical Council of India. Following the current trends of clinically oriented study of Anatomy,
I have adopted a parallel approach of imparting basic embryological knowledge to students and simultaneously providing
them its applied aspects.
To help students score high in examinations the text is written in simple language. It is arranged in easily understandable
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small sections. While embryological details of little clinical relevance, phylogenetic discussions, and comparative analogies
have been either omitted or described in brief, all clinically important topics are described in detail. Because of increasingly
significant role of molecular biology and genetics in embryology and study of birth defects, the basic molecular and genetic
principles are discussed throughout the text. In addition, a separate chapter on medical genetics has been added. The tables
and flowcharts given in the book summarize important and complex information into digestible knowledge capsules.
Multiple choice questions have been given chapter-by-chapter at the end of the book to test the level of understanding and
memory recall of the students. The numerous simple four-color illustrations and clinical photographs further assist in fast
comprehension and retention of complicated information. All the illustrations are drawn by the author himself to ensure accuracy.
Throughout the preparation of this book one thing I have kept in mind is that thorough knowledge of embryology is
required by Clinicians, especially Gynecologists, Pediatricians, and Pediatric Surgeons for physical examination, prenatal
diagnostic tests, and surgical procedures. Therefore, embryological events relevant to prenatal diagnostic and surgical
procedures are clinically correlated throughout the text. Further, patient-oriented problems and their embryological and
genetic basis are presented at the end of each chapter for problem-based learning so that the students could use their
embryological knowledge in clinical situations. Moreover, keeping in mind the relevance of embryological knowledge
in day-to-day clinical practice, a separate chapter on developmental events during the entire period of gestation and their
application in clinical practice is given at the end of the book.
I pay my heartfelt tribute to all the authors of various embryology books, especially Developing Human: Clinically Oriented
Embryology, 8th edition by Keith L Moore and TVN Persaud, which I have consulted during the preparation of this book.
From Developing Human and few other books, some photographs have been used in this book after obtaining due permission
from concerned authorities (please refer to page 331 for Figure Credits).
As a teacher, I have tried my best to make the book easy to understand and interesting to read. For further improvement
of this book, I would greatly welcome comments and suggestions from the readers. All these comments and suggestions
can be e-mailed at indiacontact@elsevier.com and drvishramsingh@gmail.com.
‘Mind perceives new ideas best only when put to test.’

Vishram Singh

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 Acknowledgments

At the outset, I express my gratitude to Dr P Mahalingam, CMD and Hon. Chancellor, Shri VP Gupta, Registrar,
and Dr Yogesh Tripathi, Hon. Vice Chancellor, Santosh University and Dr PS Dhoot, Dean, Santosh Medical College,
Ghaziabad, NCR, Delhi for providing an appropriate academic atmosphere in the university campus and encouragement
which helped me in preparing 2nd Edition of this book.
I sincerely thank all my colleagues in the Department for their assistance.
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I am really indebted to Dr Deepa Singh, Associate Professor Anatomy, Himalayan Institute of Medical Sciences (HIMS),
Dehradun, Uttarakhand; Dr Preeti Srivastava, Associate Professor, NDMC Medical College and Hindu Rao Hospital,
Delhi; and D Krishna Chaitanya Reddy, PhD Scholar, Department of Anatomy, Santosh University for reviewing the final
proofs sincerely.
I gratefully acknowledge the feedback and support received from fellow colleagues in Anatomy of various medical institu-
tions in India and abroad as well, particularly,
• Professors PK Sharma (Head of the Department) Era’s Lucknow and Punita Manik, King George’s Medical College, Lucknow.
• Professors NC Goel and AK Srivastava (Heads of the Department), Hind Institute of Medical Sciences, Barabanki,
Lucknow and Sitapur, UP, respectively.
• Professor Amit Kumar Saxena (Head of the Department), SGT Medical College, Budhera, Gurgaon, Haryana.
• Professor Poonam Kharb, SMS&R, Greater Noida, UP.
• Professor TC Singel (Head of the Department), BJ Medical College, Udaipur, Rajasthan.
• Professor TS Roy (Head of the Department) and Dr Ritu Sehgal, AIIMS, New Delhi.
• Professors RK Suri (Director Professor), and Hitendra Loh, Vardhman Mahavir Medical College and Safdarjang Hospital,
New Delhi.
• Professor Veena Bharihoke (Head of the Department), Rama Medical College, Hapur, Ghaziabad.
• Professor SL Jethani (Dean and Head of the Department), and Dr Aksh Dubey, Himalayan Institute of Medical Sciences,
Jolly Grant, Dehradun.
• Professor SK Jain (Head of the Department), Teerthanker Mahaveer Medical College & Research Centre, Moradabad, UP.
• Professor SD Joshi (Dean and Head of the Department), Sri Aurobindo Institute of Medical Sciences, Indore, MP.
• Professors Renu Mishra (Head of Department), and Vinay Kumar, Saraswathi Institute of Medical Sciences, Hapur, UP.
I eulogize the patience of my daughter, Dr Rashi Singh, son, Dr Gaurav Singh and daughter-in-law, Anupama Singh, for
helping me in the preparation of this manuscript.
Lastly, I gratefully acknowledge the help and cooperation received from my publisher, RELX India Pvt. Ltd., especially
Shabina Nasim (Sr Project Manager–Education Solutions), Renu Rawat (Manager–Content Strategy), Arvind Koul
(Content Strategist), and Goldy Bhatnagar (Sr Content Development Specialist).
Vishram Singh

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 List of Animations

1. Ovulation 25. Development of Aortic Arch Arteries

2. Fertilization 26. Remodeling of Vitelline and Umbilical Veins
3. Cleavage 27. Remodeling of Cardinal Veins Formation of Inferior
4. Implantation Vena Cava
5. Extraembryonic Structures
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28. Fetal and Neonatal Circulation
6/21/2012 3:50:09 PM

6. Gastrulation 29. Formation of Gut Tube

7. Formation of Notochord 30. Development of Foregut
8. Body Folding 31. Development of Midgut
9. Neurulation 32. Development of Hindgut
10. Secondary Neurulation 33. Development of Kidneys
11. Formation of Neural Crest 34. Development of Urogenital Sinus
12. Development of Lungs 35. Development of Gonadal Ridges
13. Development of Body Cavities and Diaphragm 36. Development of Testes
14. Formation of Primitive Heart Tube 37. Development of Genital Ducts in Males
15. Contribution of First and Second Heart Fields 38. Development of Ovaries
16. Looping of Primitive Heart Tube 39. Development of Genital Ducts in Females
17. Partitioning of AV Canal 40. Development of External Genitalia
18. Partitioning of Atrium 41. Repositioning of Gonads
19. Realignment of Heart Chambers 42. Development of Pharyngeal Apparatus
20. Partitioning of Ventricle 43. Development of Face
21. Positioning of Outflow Tract 44. Development of Palate
22. Formation of Membranous Interventricular Septum 45. Development of Eyes
23. Development of Semilunar Valves 46. Development of Ears
24. Formation of Blood Islands and Primitive Vessels 47. Development of Limbs

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 Contents

Preface to the Second Edition vii

Preface to the First Edition ix
Acknowledgments xi
VS-Chapter-06.indd 71 List of Animations 6/21/2012 3:50:09 PM xv
1 Introduction and History of Embryology 1
2 Reproductive System 10
3 Cell Division and Gametogenesis 22
4 Fertilization and Formation of Germ Layers 37
5 Primitive Streak, Notochord, Neural Tube,
Intraembryonic Mesoderm, and Folding of Embryo 50
6 Extraembryonic Membranes, Placenta, and Multiple Pregnancy 63
7 Integumentary System and Mammary Glands 85
8 Skeletal System 94
9 Muscular System 114
10 Pharyngeal Apparatus 121
11 Development of Tongue and Thyroid Gland 134
12 Development of Face, Nose, and Palate 142
13 Digestive Tract 153
14 Major Digestive Glands and Spleen 172
15 Development of Oral Cavity (Mouth), Salivary Glands, and Teeth 183
16 Respiratory System 193
17 Body Cavities and Diaphragm 203
18 Development of Heart 214
19 Development of Blood Vessels 231
20 Development of Urinary System 254
21 Genital System 268

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xiv Contents

22 Development of Nervous System 288

23 Pituitary, Pineal, and Adrenal Glands 299
24 Eye and Ear 304
25 Medical Genetics 319
26 Application of Embryology in Clinical Practice 334
Appendix 343
Multiple Choice Questions 347
Index 361

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 Introduction and History
of Embryology
Learning Objectives
After studying this chapter, the student should be able to:
• Define embryology and tell how it differs from developmental
anatomy.
• Divide prenatal development into preembryonic, embryonic
and fetal periods.
• Enumerate 5 periods of postnatal development.
Overview
Embryology is the science that deals with the development and
growth of an individual before birth. It begins with fertilization
of an oocyte (ovum) by a sperm and culminates with the birth
of the baby. The entire period of development from fertilization
to birth is termed prenatal development. The period of prena-
tal development is also called gestation period/pregnancy.
(Pregnancy is described in detail in Chapter 26, p. 334.) The
development of an individual continues even after birth up to
the age of 25 years. This period of development is termed post-
natal development.
N.B. The term pregnancy used by clinicians refers to state of
female carrying an unborn baby (products of conception) inside
her (Latin: Pregnancy, which means carrying products of con-
ception). It includes 38 weeks, extending from fertilization to
the birth.
Prenatal Development
The prenatal development is a fascinating and awe-
some event. It begins with a single cell - the zygote
(fertilized ovum) and culminates after 9 months (38
weeks or 266 days) with a complex organism - the
newborn - made of billions of cells. This involves a
process called morphogenesis, which includes cell
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division, transformation or specialization, migration,
and even programmed cell death (apoptosis).
During morphogenesis, genetic or environmental
factors may affect the normal development of the baby
and cause congenital anomalies.
Thus embryology helps us in understanding not
only the rationale of structure and functions of each
body system but also the factors responsible for causing
congenital anomalies. The appreciation of these factors
may assist the clinicians in preventing and treating
such anomalies.
Periods of Prenatal Development
The prenatal development is divided into three peri-
ods: (a) preembryonic period, (b) embryonic period,
and (c) fetal period.
1. Preembryonic period: It extends from concep-
tion (fertilization) to the end of the 2nd week of
intrauterine life (IUL).
2. Embryonic period: It extends from beginning of
the 3rd week to the end of 8th week of IUL.
3. Fetal period: It extends from beginning of the
9th week to birth a baby.
The periods of prenatal development and events
occurring during these periods are shown in Table 1.1.
N.B. Clinically the prenatal development is divided into two
periods: (a) embryonic period and (b) fetal period.
1. Embryonic period: It extends from fertilization to the end of
the 8th week and the developing organism is called an embryo.
2. Fetal period: It extends from beginning of the 9th week
(3rd month) until the birth.
Postnatal Development
The development of an individual from birth to about
25 years is called postnatal development.
2 Textbook of Clinical Embryology

do not stay the same during this period. As the child

Table 1.1 M
 orphological events occurring during
grows, the rate of growth slows down; however, just
preembryonic, embryonic, and fetal
periods of prenatal development before puberty the growth accelerates. This is called
prepubertal growth spurt. The medical subject deal-
Period Morphological events ing with the care of children in health and disease is
1. Preembryonic • Formation of zygote termed pediatrics.
period (from • Initiation of cleavage
fertilization to • Implantation Puberty (Latin: Pubertas, which means
2nd week) • Formation of bilaminar germ disc
development of sex characteristics)
2. Embryonic period • Formation of placenta, umbilical
(from 3rd week to cord, and extraembryonic The puberty period ranges from 12 to 15 years in fe-
8th week) membranes males and 13 to 16 years in males. During this period,
• Differentiation of germ layers
there is a very rapid physical growth and development of
into specific body organs
secondary sexual characters, and the capability of sexual
3. Fetal period (from • Growth and specialization of the reproduction is attained. The growth during puberty is
9th week to birth) body structures
dependent on the interaction of growth hormone (insu-
lin-like growth factor 1 [IGF-1]) and sex steroids.

Periods of Postnatal Development Adolescence

The postnatal development is divided into the following
five periods:
1. Infancy (from birth to 1 year of age)
2. Childhood (from 2 to 12 years of age)
3. Puberty (from 13 to 16 years of age)
4. Adolescence (from 17 to 18 years of age)
5. Adulthood (from 19 to 25 years of age)
Infancy
The infancy period ranges from birth to 1 year of age
and the newborn during this period is termed infant.
The first 4 weeks of this period are very critical for the
survival of the newborn because the transition from
intrauterine to the extrauterine existence requires
many changes especially in the cardiovascular and re-
spiratory systems. During this period there is a rapid
growth of the body. This period is called neonatal
period and the newborn during this period is termed
neonate. If a newborn survives first few hours after
birth, his/her chances of survival are usually good. The
care of the baby during the neonatal period is termed
neonatology.
N.B.
l The term perinatal period used by clinicians extends from 28th
The adolescence period ranges from 17 to 18 years.
This period is characterized by rapid physical growth
and sexual maturation. The gonads begin to secrete
testosterone and estrogen. During this period the abil-
ity to reproduce is achieved.
Adulthood (Latin: Adultus, which means
grown up)
The adulthood period ranges from 19 to 25 years.
During this period full growth and development of
body organs including ossification of bones is virtually
completed.
Subdivisions of Embryology
General Embryology
It deals with the development of an individual during
first 8 weeks after fertilization (i.e., It deals with pre-
embryonic and embryonic periods). During this pe-
riod a single cell called zygote (fertilized ovum) is
converted into a form that externally resembles the
features of an adult individual and all organs and sys-
tems are formed.

week of pregnancy to the end of 6th day after birth. Systemic Embryology
It deals with the functional maturation of various or-
Childhood gans and systems that are formed during the embryonic
period.
The period of childhood extends from beginning of the
2nd year to the age of 12 years. The care of children Descriptive Embryology
during this period is exciting because of the constancy It deals with the structure of different organs at various
of change in their growth and development. Children stages of development.

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 Introduction and History of Embryology 3

Comparative Embryology
It deals with the study of embryos in various species of
animals.

Experimental Embryology
It deals with the results obtained from experiments of
living embryos/fetuses of the lower animals.

Chemical Embryology
It deals with the biochemical aspect of the prenatal
Fig. 1.1 ​Dolly, the first cloned sheep.
development.

Teratology (c) More recently, the cloning of a human embryo

It is a branch of embryology that is concerned with the has been reported.
congenital anomalies or birth defects. i.e. It deals with 5. Stem cell therapy: Stem cells are cells found in
abnormal embryonic and fetal development. Teratol- multicellular organisms. These cells have the abil-
ogy is described in detail in Chapter 26, p. 338. ity to renew themselves and differentiate into a
diverse range of specialized cell types. There are
two broad types of mammalian stem cells:
Recent Advances in Embryology
(a) Embryonic stem cells, which are isolated from the
1. Prenatal diagnosis: It is the detection of congeni- inner cell mass of the blastocysts (Fig. 1.2).
tal abnormalities in an unborn child. Some of the These are pluripotent, i.e., they have the abil-
techniques used for this purpose are as follows: ity to form different cell types.
(a) Amniocentesis (b) Adult stem cells, which are found in adult tissues,
(b) Chorionic villous sampling e.g., bone marrow. These cells are restricted in
(c) Ultrasonography their ability to form different cell types and
(d) Fetoscopy therefore are multipotent, not pluripotent.
(e) Fetal blood sampling N.B. The isolation and programmed culture of human embryonic
(f) Maternal serum screening stem cells hold a great potential for the treatment of degenerative,
(g) MRI malignant, and genetic diseases. (The embryonic stem cells are plu-
2. In vitro fertilization: In vitro fertilization (IVF) ripotent. They are capable of self-renewal and are able to differen-
tiate into specialized cell types.) Ruth R. Faden of Johns Hopkins
of human ova and embryo transfer in the uterus University once said that we believe the obligation to relieve
has now become a standard procedure throughout human suffering, which binds us all and justifies the instrumental
the world to solve the problems of infertility. On use in early embryonic life.
25 July 1978, Louis Joy Brown, the first test tube
baby, was born to Leslie Brown.
3. Gene therapy: It deals with the replacement of a
deficient gene product or correction of an abnor-
mal gene. It can be done in vitro or in vivo.
4. Cloning: The advancement in molecular biology
has led to many sophisticated techniques that are
now widely used in research laboratories for genetic
regulation of morphogenesis. Now the researchers
have started understanding how, when, and where
selected genes are activated and expressed in the
embryo during development. For example:
(a) Now cloning is possible. The first mammal
clone, Dolly the sheep, was cloned in 1997
(Fig. 1.1) by using the technique of somatic
cell nuclear transfer.
(b) The interest in human cloning has generated a
considerable debate because of social, moral,
ethical, and legal implications. Fig. 1.2 ​Embryonic stem cells.

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4 Textbook of Clinical Embryology

(a) Embryo comes into existence from conjuga-

Utility and Scope of Embryology in Medicine
tion of blood and semen during the period
A thorough knowledge of embryology is important for favorable for conception after sexual
the following reasons. intercourse.
(b) Developmental stages of an embryo are as
1. It explains the positions and relations of various
under:
organs and neurovascular structures in adult gross
anatomy. ● 1-day-old embryo Formation of Kalada
2. It helps to understand the cause of development of ● After 7 nights Formation of vesicle
various congenital anomalies such as tracheoesoph-
● After 1 month Formation of spherical mass
ageal fistula, polycystic kidney, and subhepatic
● After 2 months Formation of head
cecum.
● After 3 months Formation of limbs
The knowledge of various factors causing con-
genital anomalies (such as use of alcohol, smoking,
3. Hippocrates (460–377 BC) (Fig. 1.3) gave the
drugs, viral infections, and teratogens) can be use-
following advice to understand the development of
ful in preventing their occurrence by rendering
the embryo:
advice and adopting preventive measures.
Take 20 or more eggs and let them be incubated
3. Some aspects of general embryology such as game-
by two or more hens. Then from the second day to
togenesis, fertilization, and implantation are of
the day of hatching remove one egg every day,
great importance to understand the cause of infer-
break it, and examine it. You will exactly see how
tility and its management. It also helps in family
the embryo develops. This development of chick
planning.
embryo can be similar to that of man.
4. It forms the basis of concept of growth, repair, and
4. Aristotle (384–322 BC) (Fig. 1.4) wrote a treatise
regeneration of tissues, and understanding of the
on embryology in which he described the develop-
development of various embryonic tumors.
ment of the chick and other embryos. Aristotle is
5. Ex utero surgery is nowadays possible to treat cer-
regarded as the Founder of Embryology. According to
tain congenital anomalies, namely, congenital dia-
him, an embryo develops from a formless mass,
phragmatic hernias and repair of spina bifida, only
which he described as a fully concocted seed with a
due to in-depth study of embryology.
nutritive soul and all body parts. The mass arose
6. It provides the basis for medical termination of
from menstrual blood after activation by semen.
pregnancy in various congenital diseases, which are
5. Claudeus Galen (AD 130–201) (Fig. 1.5) wrote a
incompatible with life.
book on the formation of the fetus in which he
7. It provides insight for use of molecular biology for
described the development and nutrition of fetuses.
genetic regulation of human development.
He also described structures that are now called
allantois, amnion, and placenta.
History of Embryology
The following text provides only a brief account of his-
tory of embryology as a mark of respect to some leg-
ends who have a significant contribution in the field of
embryology.
“If I have seen further, it is by standing on the
shoulders of the earlier giants.”
–Sir Isaac Newton

1. Ancient Egyptians (3000 BC) knew about the

methods of incubation of eggs of the birds. They
also believed that Aten, the Sun god, is the creator
of germ in woman and seed in man and gives life to
the baby in the body of mother.
2. The Garbha Upnishad, an ancient scripture of
Hindus (written in around 1416 BC), describes
Fig. 1.3 ​Hippocrates (460–377 BC).
following ideas about embryo:

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Fig. 1.4 ​Aristotle (384–322 BC).
Fig. 1.5 ​Claudius Galenus (130–201 AD).
6. Samuel-el-Yehudi (second century AD) described
six stages in the formation of embryo from a “form-
less, rolled-up thing” to a “child whose months
have been completed.”
7. Quran (seventh century AD), the holy book of the
Muslims, describes that the human beings are pro-
duced from a mixture of secretions from the male
and female. It also mentions that the human being
is created from nufla (small drop). It also states that
the resulting organism settles in the womb like a
seed 6 days after its beginning. The early embryo
resembles a leech and later it resembles a “chewed
substance.”
8. Leonardo da Vinci (1452–1519) (Fig. 1.6) made
accurate drawings of dissections of uterus of preg-
nant women containing fetuses (Fig. 1.7).
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Introduction and History of Embryology 5
Fig. 1.6 ​Leonardo da Vinci (1452–1519).
Fig. 1.7 ​Reproduction in Leonardo da Vinci’s drawing made
in the fifteenth century AD to show a fetus in the uterus.
Modified from figure published in Publication The Developing
Human: Clinically Oriented Embryology, 8th edition by Keith L.
Moore and T.V.N. Persaud, ISBN: 9781416037064, page 9,
Fig. 1.4, Copyright Elsevier, 2008.
9. William Harvey (1578–1657) believed that male
seeds or sperms after entering the womb or uterus
get metamorphosed into an egg-like substance
that gives rise to an embryo.
10. Regnier de Graaf was the first to observe vesicular
ovarian follicles in 1672 with the help of simple
microscopes, which are still called Graafian follicles.
11. Johan Ham van Arnheim and Anton van
Leeuwenhoek were the first to observe a human
sperm. They thought that sperms contain a minia-
ture preformed human being that gets enlarged
when sperm is deposited in the female genital tract.
Other embryologists at this time thought that
the oocyte contained a miniature human being
6 Textbook of Clinical Embryology

Fig. 1.9 ​Karl Ernst von Baer.

Fig. 1.8 ​Seventeenth century drawing of a sperm by Hart-

soeker. Modified from figure published in Publication The
Developing Human: Clinically Oriented Embryology, 8th edition
by Keith L. Moore and T.V.N. Persaud, ISBN: 9781416037064,
page 10, Fig. 1.6, Copyright Elsevier, 2008.

that enlarged when it was stimulated by a sperm

(Fig. 1.8).
12. Caspar Friedrich Wolff (1759) proposed the layer
concept, i.e., zygote produces layers from which the
embryo develops. His ideas formed the basis of the
theory of epigenesis, which states that the develop-
ment results from growth and differentiation of
specialized cells. The mesonephros and mesoneph-
ric duct are called Wolffian body and Wolffian
duct, respectively, after his name.
13. Lazaro Spallanzani (1775) said that both oocyte
and sperm are necessary for initiating the develop-
ment of an individual.
14. Heinrich Christian Pander discovered the three
germ layers in 1817.
15. Etienne Saint Hilaire and Isidore Saint Hilaire
made the significant studies of abnormal develop-
ment in 1818, initiating what we now know as the
science of teratology.
16. Karl Ernst von Baer (Fig. 1.9) described the oocyte
in the ovarian follicle of a dog in 1827. He also noted
cleaving zygote in uterine tube and blastocysts in the
uterus. His study provided new knowledge about the
origin of tissues and organs from three germ layers of
the embryo, which formulated two embryological
concepts: (a) corresponding stages of embryonic development
and (b) that general characteristics precede specific ones. For
his significant and far-reaching contributions, he is
regarded as the Father of Modern Embryology.
Fig. 1.10 ​Patrick Steptoe.
17. Hans Spemann (1869–1941) discovered the phe-
nomenon of primary induction, i.e., how one tissue
determines the fate of another. He was awarded
Nobel Prize in 1935.
18. Patrick Steptoe and Robert G Edwards (Fig. 1.10)
pioneered the development of the technique of in
vitro fertilization. Louise Brown is the first test tube
baby born in 1978.
19. James Till (1931–) (Fig. 1.11) along with Ernest
McCulloch discovered stem cells in 1960. Since the
discovery of stem cells by James Till, the hope for
treatment of terminal diseases has become enormous.
20. Ian Wilmut (1944), an English embryologist
(Fig. 1.12), is best known for leading a team that cloned
a mammal from an adult somatic cell in 1996 – a
Finnish Dorset lamb named Dolly (Fig. 1.1). The clon-
ing is a cell, cell product, or organism that is genetically
identical to the unit or individual from which it was
derived. Clones are duplicates of each other resembling
in anatomy and physiology.

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Fig. 1.11 ​James Till.
Fig. 1.12 ​Ian Wilmut.
Embryological Terms
Most of the terms used in embryology are of Latin (L.)
or Greek (Gr.) origin. The following text lists only with
those terms that are commonly used.
1. Oocyte (L. Ovum 5 egg): Female germ or sex cells
produced by ovaries. Mature oocyte is called sec-
ondary oocyte.
2. Sperm (Gr. Sperma 5 seed): Male germ cells pro-
duced by testes.
3. Zygote: Cell formed by union of a sperm and sec-
ondary oocyte (ovum). The zygote is the earliest
stage of embryo (i.e., the beginning of the new
human being).
4. Conceptus: Product of conception, i.e., embryo
along with its extraembryonic membranes.
5. Cleavage: Series of mitotic divisions of the zygote
to form early embryonic cells – the blastomeres.
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Introduction and History of Embryology 7
6. Morula (L. Morus 5 mulberry): Solid ball of 12–
32 cells (blastomeres) formed 3–4 days after fertil-
ization, just at the time when embryo enters the
uterus.
7. Blastocyst (Gr. Blastos 5 bud, Kystis 5 bladder):
It forms at late morula stage when fluid passes into
intercellular spaces between the inner and outer
layers of cells and forms a fluid-filled cavity. The
blastocyst is divided into two parts: an outer layer
of small, slightly flattened cells called trophoblasts
and inner cell mass (embryoblast) consisting of a
group of larger polyhedral cells.
The cavity of blastocyst (blastocele) separates
the trophoblast from the inner cell mass except for
a small area where they are in contact.
8. Implantation: Attachment and subsequent embed-
ding of blastocyst into uterine endometrium, where
it develops during gestation. Implantation occurs
between fifth and seventh day after fertilization.
9. Gastrulation: Formation of three germ layers (ecto-
derm, mesoderm, and endoderm) in the embryo. It
is the most characteristic event during the third
week of gestation.
10. Neurulation (Gr. Neuron 5 nerve): Process by
which neural plate forms the neural tube.
11. Embryo (Gr. Embryon): Developing human from
conception to eighth week in uterus. This period is
called embryonic period (or period of organogene-
sis). By the end of this period primordia of all the
major structures of the body are formed.
12. Primordium (L. Primus 5 first 1 Ordior 5 to
begin): Beginning or first discernible indication of
an organ or structure.
13. Fetus (L. Unborn 5 offspring): Developing human
from ninth week to birth. During this period (fetal
period), differentiation and growth of the tissues
and organs formed during the embryonic period
takes place.
14. Abortion (L. Aboriri 5 to miscarry): Expulsion of
a conceptus (embryo or fetus) before it is unable,
i.e., capable of living outside the uterus.
15. Gestation (L. Gestatio 5 bearing, carrying in the
womb): The duration of embryo in the uterus from
fertilization of the ovum until delivery (the period
of normal pregnancy).
16. Gestational age: The gestational age of embryo/
fetus is calculated from presumed first day of
the last normal menstrual period. The oocyte is
not fertilized until approximately 14 days (2 weeks
after the preceding menstruation); hence, the fer-
tilization age of an embryo or fetus is 14 days
less than the gestation age.
8 Textbook of Clinical Embryology

GOLDEN FACTS TO REMEMBER

 Founder of embryology Aristotle (384–322 BC)

 Father of modern embryology
 First individuals to observe human sperm
 Carnegie collection of embryos is now in
 First test tube baby
 First mammal cloned
 Inventor of first mammal cloning
 Most famous Siamese twins
 Stem cells were discovered in
 Longest period of prenatal development
 Earliest period of extrauterine life
 Fertilization age
Karl Ernst von Baer
Johan Ham van Arnheim and Anton van Leeuwenhoek
National Museum of Health and Medicine in the Armed Forces
Institute of Pathology in Washington DC
Louise Brown born in 1978
Dolly, the female domestic sheep (5 July 1996 to 14 February 2003)
Ian Wilmut (1944)
Chang and Eng Bunker (born in 1811 in Siam [Thailand])
1960 by James Till
Fetal period
Infancy (first year after birth)
Gestational age – 14 days

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 Introduction and History of Embryology 9

CLINICAL PROBLEMS

1. How do the terms zygote and conceptus differ?

2. The division of prenatal development differs among anatomists and clinicians. How?
3. What do you understand by the term teratology?
4. What are stem cells? Which diseases are likely to be benefited by the stem cells?

CLINICAL PROBLEM SOLUTIONS

1. The zygote is a diploid single cell formed after fertilization by the union of haploid male and female gametes.
It is also called a single cell embryo.
The term conceptus refers to the product of conception, i.e., embryo and associated extraembryonic membranes.
2. The anatomists divide prenatal development into 3 periods, viz. preembryonic, embryonic and fetal, while clinicians
divide it into 2 periods, viz. embryonic (from fertilization to 8th week) and fetal (from 9th week to birth).
3. Teratology is the branch of embryology that deals with the congenital anomalies and defects.
4. The stem cells are undifferentiated cells, which are capable of multiplication and differentiation into all types of
specialized cells in the body. The cells of embryoblast are capable of generating all the three germ layers: ectoderm,
mesoderm, and endoderm. Hence, cells of embryoblast (inner cell mass) are termed embryonic stem cells. These
can be kept in an undifferentiated state in culture medium. By using growth factors, these can be made to form dif-
ferent tissue cells, e.g., muscle cells, neurons, and blood cells. The diseases that are likely to be benefited by stem cells
are Parkinson’s disease, Alzheimer’s disease, spinal cord injuries, sickle cell anemia, etc.

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 Reproductive System
Learning Objectives
After studying this chapter, the student should be able to:
• Enumerate the primary and secondary reproductive organs
of a male.
• Enumerate the components of the male genital tract.
• Enumerate the primary and secondary reproductive organs
of a female.
• Enumerate the components of the female genital tract.
• Describe menstrual and ovarian cycles in brief.
Male Reproductive System
Overview
The primary reproductive organ in males is testis. The secondary
reproductive organs in males are scrotum, epididymis, ductus
deferens, seminal vesicles, urethra, prostate gland, bulbourethral
glands, and penis (Fig. 2.1). The male genital tract consists of vasa
efferentia (efferent ductules), epididymis, vas deferens, ejacula-
tory duct, and urethra. The male genital tract carries sperms pro-
duced in the testis to the urethra, from where the sperms are
deposited in the vagina during copulation (intercourse) .
Testes
Testes are a pair of ovoid organs within the scrotum
that produce sperms and testosterone. Each testis is
4-5 cm long lying within the scrotum, and is sus-
pended in the scrotum by the spermatic cord. The
spermatic cord provides vascular, lymphatic, and nerve
supply to the testes, and provides passage to the vas
deferens. The outer part of each testis is made up of a
thick, white capsule - the tunica albuginea (Fig . 2.2).
The fibrous septum from the capsule extends inside and
divides each testis into 200-300 cone-shaped lobules.
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Each lobule contains 2-4 convoluted seminiferous
tubules. The epithelial lining of the walls of these
tubules contain cells that develop into spermatozoa
through cell division. Surrounding the tubules are
interstitial cells of Leydig, which secrete male
hormone - the testosterone .
The seminiferous tubules empty their secretion (e.g.,
spermatozoa) into tubular network - the rete testis,
which in turn empty into 15-20 efferent ductules .
The efferent ductules enter into the epididymis to form
the duct of epididymis.
Epididymis
Epididymis is a comma-shaped structure lying posteri-
orly and slightly lateral to each testis with vas deferens
along its medial side. It consists of a single convoluted
duct (duct of epididymis) formed by the union of the
efferent ductules of the testis. Within the duct of epi-
didymis, the spermatozoa mature, develop some motil-
ity, and learn a little bit of swimming. The spermato-
zoa show circular or even forward directional
movements.
Vas Deferens
Vas deferens is a thick-walled muscular tube, about
45 cm (18 inches) long, which begins at the tail of the
epididymis as the direct continuation of the duct of the
epididymis. It runs upward along with vessels within
the spermatic cord. The terminal part of each vas def-
erens is sacculated and is called ampulla of vas defer-
ens . It serves as a reservoir of sperm and tubular fluid .
The terminal narrow part of vas deferens joins the duct
of seminal vesicle to form the ejaculatory duct at the
base of the prostate gland. The main function of vas defer-
ens is to transport spermatozoa from the epididymis to ejacula-
tory duct. Peristaltic contractions of smooth muscle help
 Reproductive System 11

Urinary bladder

Ampulla of vas deferens

Seminal vesicle
Prostate gland
Ejaculatory duct
Bulbourethral glands
Penis (Cowper’s glands)

Urethra
Vas deferens
Duct of
epididymis Vasa efferentia (efferent
ductules of testis)
Scrotum
Testis

Fig. 2.1 ​Male reproductive system.

Lobules of epididymis

Fibrous septa
Efferent ductules
(15–20 in number)
Convoluted seminiferous Duct of epididymis
tubules (2–3 in each lobule)

Tunica albuginea Rete testis

Vas deferens

Lobules of
testis (200–300)

Fig. 2.2 ​Schematic vertical section of the testis showing the basic structure of testis, epididymis, and vas deferens.

in propelling the semen. The vas deferens is cord like
when grasped between thumb and index finger because
of its thick wall and small lumen.
Seminal Vesicles and Ejaculatory Ducts
The seminal vesicle (5 cm long) is a sacculated coiled
tube adjacent to ampulla of each vas deferens. The paired
seminal vesicles secrete a major portion of volume of
ejaculate. These are located behind the bladder near the
prostate gland. Each vesicle ends in a small duct that
joins ampulla of vas deferens to form an ejaculatory
duct. The two ejaculatory ducts are slender tubes that
open into the prostatic part of the urethra. The secretion
of seminal vesicles is thick and mucous like. It contains
fructose that provides nutrition to sperms.
Prostate Gland
Prostate gland is a pyramidal fibromuscular gland of
about the size of a chestnut. It is gray to reddish in
color, and consists mainly of glandular and muscular
tissue.
The prostate gland surrounds the proximal part of
the urethra and two ejaculatory ducts. It is enclosed by
a thin but strong fibrous capsule. The capsule is con-
tinuous with several fibromuscular partitions. The
prostatic glands secrete prostatic fluid, which is
poured into the prostatic urethra through 10–20 ducts.
The prostatic fluid contains acid phosphatase, fibrino-
lysin, citric acid, amylase, prostate specific antigen, and
prostaglandins. The prostatic fluid forms the bulk of
the semen (i.e., ejaculate).

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12 Textbook of Clinical Embryology

of 100 million per mL. It is white and opalescent. The approximate

Bulbourethral Glands (Cowper Glands)
Bulbourethral glands, also called Cowper glands, are two
yellow, pea-sized glands located on each side of membra-
nous urethra. These glands secrete alkaline mucus that is
poured into the penile urethra just before ejaculation of
the semen. The secretion of these glands mixes with
sperms and other glandular secretions to form semen.
They contribute 5%–6% of total ejaculate. The alkaline
nature of these secretions protects sperms against the
acidity of the urethra and vagina. The secretions of bul-
bourethral glands also provide lubrication during coitus.
contribution by various reproductive glands is as under:
l Seminal vesicles: 60%
l Prostate: 30%
l Testes: 5%
l Bulbourethral glands: 5%
The thin milky secretion of the prostate gland is alkaline in nature
and neutralizes the acidic pH of the vagina. The movement of
sperms is best at a pH of 6–6.5, whereas the vaginal pH is about
3.5–4.
The enzymes of prostatic secretion break down the coagulated
proteins secreted by seminal vesicles and make the semen more
liquid.

Penis Female Reproductive Organs

Penis is the male organ of copulation. It is pendulous

and visibly consists of glans penis and shaft of penis.
Two of erectile columns forming the dorsal portion and
the sides of penis are called corpora cavernosa. The
third erectile column forming the ventral portion of
penis is termed corpus spongiosum. The distal end of
corpus spongiosum expands to form a triangular en-
largement called glans penis. Urethra travels through
the corpus spongiosum and opens as external urethral
orifice on the tip of glans penis.
N.B. Semen: It is the fluid ejaculated by penis into the vagina at
the time of orgasm. It consists of sperms produced by seminiferous
tubules of testes and secretions of seminal vesicles, prostate gland,
and bulbourethral glands. The average volume of ejaculate is 2.5–
3.5 mL. Semen has a pH of 7.35–7.5, with an average sperm count
Overview
The primary reproductive organ in females is ovary. The sec-
ondary reproductive organs in females are uterine tubes,
uterus, vagina, vulva, and vestibular glands. The female genital
tract consists of fallopian tube, uterus, and vagina (Fig. 2.3). The
female genital tract provides the site of fertilization and site for
the development of the embryo.
Ovaries
Ovaries are a pair of small ovoid organs (3 cm long
3 2 cm wide 3 1 cm thick) of about the size and
shape of an almond. They are situated in the lateral
wall of the lesser pelvis on either side of the uterus

Parts of uterine tube

Intramural Ampulla
part Infundibulum
Isthmus

Fimbria of
Perimetrium uterine tube
Myometrium Ovary
Endometrium Round ligament
of ovary
Uterine cavity

Cervical canal Vaginal fornix

Vagina

Fig. 2.3 ​Female reproductive system.

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below and behind the uterine tubes. Each ovary is at-
tached to the upper part of the uterus by the round
ligament of the ovary. One end of each ovary is in
contact with the fimbria of the uterine tube.
The ovary consists of a thick cortex surrounding a very
vascular medulla. The cortex surrounding the medulla
consists of a framework of connective tissue covered by
the germinal epithelium. Before puberty, it contains
numerous primordial follicles. After puberty, it con-
tains ovarian follicles in various stages of maturity. Each
follicle contains an ovum. Till puberty the ovaries remain
inactive but stroma still contains immature follicles.
During childbearing age, one ovarian follicle ma-
tures and ruptures to release its ovum into the perito-
neal cavity. This process is called ovulation and recurs
(ovarian cycle) throughout the reproductive life of a
female. If a woman becomes pregnant, the ovarian cycle
stops temporarily.
Ovarian Cycle (Figs 2.4 and 2.5)
The ovarian cycle is the cyclic release of ovum from
the ovary. This cycle is controlled by hormones secreted
by the pituitary gland. At the onset of puberty, the
pituitary gland secretes follicle stimulating hormone
(FSH). Under the influence of this hormone, the pri-
mordial follicles in the ovary start growing. The grow-
ing/maturing follicles produce hormone estrogen.
Only one follicle reaches the full development and
forms Graafian follicle. Through feedback mechanism,
Corpus
albicans
Mesovarium
Primordial follicle
Primary follicles
Maturing
secondary follicle
Secondary follicle
FOLLICULAR PHASE
Fig. 2.4 ​Schematic diagram of ovary showing various stages of development of ovarian follicles, and formation of corpus luteum
and corpus albicans.
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Reproductive System 13
the increased level of estrogen hormone inhibits the
secretion of FSH from the anterior pituitary. The pitu-
itary gland also secretes luteinizing hormone (LH).
Under the influence of a large amount of LH, the
Graafian follicle bursts and ovulation takes place. The
ovum is released due to action of proteolytic enzymes
formed by the theca externa cells that cause dissolution
of capsular wall. There is plasma transudation within
the follicles. As a result, follicles swell and pressure
within them increases. Because of increased intrafol-
licular pressure and simultaneous dissolution of follicu-
lar capsular wall, follicles rupture and ovum is released
(ovulation). After ovulation, the empty follicle devel-
ops into corpus luteum, which secretes hormone
progesterone. The corpus luteum degenerates after
10 days if the ovum is not fertilized. The level of pro-
gesterone decreases, and again the pituitary gland se-
cretes FSH and a new cycle starts. Thus, the cyclic
changes in the ovary comprising of development
of ovarian follicles, ovulation, and formation of
corpus luteum constitute the ovarian cycle.
The corpus luteum persists for 2–3 months if the
ovum is fertilized. By that time placenta develops and
starts secreting progesterone and estrogen. The high
levels of these hormones in blood further suspend the
ovarian cycle during pregnancy.
N.B. The ovarian cycles normally persist throughout the repro-
ductive life of women except during pregnancy. The ovarian cycle
terminates at menopause.
LUTEAL P
HAS
E
Corpus
luteum
Cortex
Germinal
epithelium
Ovulation
Medulla Secondary
oocyte
Oocyte Graafian follicle
14 Textbook of Clinical Embryology

2. The luteal phase corresponds to the second half of

Pituitary gland the menstrual cycle. During this phase, the formation
of the corpus luteum takes place following ovula-
tion. Changes in uterine endometrium take place
Adenohypophysis due to secretion of the hormone progesterone.
N.B.
l Three important events occur during an ovarian cycle:

(a) Follicular development

FSH LH
(b) Ovulation (release of oocyte) – the most important event
(c) Formation of corpus luteum
l Output of follicular development:
Ovary Ovary
(a) Growth and development of primary oocyte
− (b) Differentiation of follicular cells
(c) Formation of zona pellucida
Growth of follicles Ovulation (d) Formation of theca folliculi (viz. theca interna and theca
externa)
(e) Formation of antrum folliculi
Estrogen Formation of corpus luteum

Uterus (Fig. 2.6)

Progesterone
Fig. 2.5 ​Ovarian cycle.
Two phases of the ovarian cycle: The ovarian cycle
is divided into two phases: (a) follicular phase and
(b) luteal phase.
1. The follicular phase corresponds to the first half of
the menstrual cycle. During this phase, follicles
develop and discharge only one mature oocyte.
Changes in the endometrium of uterus take
place due to secretion of the hormone estrogen pro-
duced by the developing follicles.
Uterus is a hollow, thick-walled muscular organ where
fetus develops. It is a pear-shaped organ, which is flat-
tened anteroposteriorly. It lies in anteverted and ante-
flexed position in the lesser pelvis.
It is about 7.5 cm long, 5 cm wide, and its walls are
about 2.5 cm thick. It weighs about 30–40 g.
It has three parts: fundus, body, and cervix.
• Fundus is the upper dome-shaped part of the uterus
above the openings of uterine tubes. It is devoid of
cavity.
• Body is the main part of the uterus where fetus
develops.
• Cervix is the lower cylindrical part of the uterus that
protrudes into the vagina.

Fundus

Uterine
tube
Uterine cavity

Body
Uterine wall

Isthmus
Internal os
Supravaginal
portion of cervix Cervical canal
Cervix
Vaginal portion of
cervix
External os
Vagina Cavity of vagina
A B
Fig. 2.6 ​Uterus: (A) external view; (B) internal view.

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 Reproductive System 15

Structure endometrial cycle, which is commonly referred to as

The uterus consists of three layers. From superficial
to deep these are perimetrium, myometrium, and
endometrium.
1. Perimetrium: It consists of peritoneum covering
the uterus.
2. Myometrium: It is the thickest layer and consists
of smooth muscle. The smooth muscle fibers are
arranged in longitudinal, oblique, transverse, and
circular layers. Hence, the wall of the uterus is very
strong. During pregnancy, the muscle fibers
undergo hyperplasia and hypertrophy. This layer
contains blood vessels and nerves; hence, it is also
called stratum vasculare.
3. Endometrium: It is the mucous lining of the body
of the uterus containing a large number of mucus-
secreting glands. It consists of three layers (Fig. 2.7).
From outside to inside these three layers are as follows:
(a) Stratum basale/basal layer: It is thin and has a
separate blood supply.
(b) Stratum spongiosum/spongy layer: It is thick and
edematous.
(c) Stratum compactum/compact layer: It is thin and
superficial toward the uterine lumen. It con-
sists of compactly arranged stromal cells.
Mnemonic: BSC 5 basal layer; spongy
layer; compact layer.
N.B. The compact and spongy layers together form stratum
functionalis (functional layer), which is sloughed off during men-
struation. The basal layer is never sloughed off.
Menstrual Cycle (Fig. 2.8)
During the reproductive life of a woman, the uterine
endometrium undergoes monthly cyclic changes called
the menstrual cycle because of menstruation (flow of
blood from the uterus) as a notable feature. At the age of
45 years, the menstruation ceases and this stage is
termed menopause. (Similar cyclic changes occur in
ovaries, which constitute the ovarian cycle, see p. 13.)
Each menstrual cycle in most of the women consists
of roughly 28 days. Day 1 is the day when the men-
strual flow starts. The ovulation occurs in the middle of
the cycle (i.e., 14th day).
Each menstrual cycle is divided into four phases on the
basis of changes that occur in the endometrium:
1. Menstrual phase
2. Proliferative phase
3. Secretary phase
4. Premenstrual phase
Clinical Correlation
1. Abnormal menstrual cycles
(a) Hypomenorrhea: It is scanty blood flow during the men-
strual cycle.
(b) Menorrhagia: It is profuse blood flow during the men-
strual cycle.
(c) Metrorrhagia: It is the occurrence of bleeding between
the menstrual cycles.
(d) Oligomenorrhea: It is reduced frequency of menstrual
cycles.
2. Amenorrhea: It is the absence of menstruation. Amenorrhea
may be of two types: primary and secondary.
(a) Primary amenorrhea: It is the condition when menstrual
bleeding does not occur after 16 years of age.
(b) Secondary amenorrhea: It is stoppage of menstrual
cycles with normally occurring menstrual cycles before.
Most common cause of amenorrhea is pregnancy.

Lining epithelium
(simple columnar, and secretory)

Stratum
compactum
Uterine
gland
Stratum
Spiral
spongiosum
artery

Stratum basale

Straight Myometrium
artery

Fig. 2.7 ​Layers of endometrium.

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16 Textbook of Clinical Embryology

Ovarian cycle

Primordial Primary Secondary

Graafian Corpus Corpus
follicle follicle follicle
follicle luteum albicans
Follicular phase Ovulation
14th day

Luteal phase
Menstrual cycle

Stratum
compactum

Stratum
spongiosum

Stratum basale

1–4 days 5–14 days 15–25 days 26–28 days

Menstrual Proliferative Secretory Premenstrual
phase phase phase phase

Fig. 2.8 ​Correlation between ovarian and menstrual cycles.

N.B. Changes in the endometrium occur as a result of hormones
(estrogen and progesterone) secreted by the ovaries (ovarian cycle),
which in turn is controlled by hormones secreted by the hypothala-
mus and pituitary gland.
1. Menstrual phase (menses) (1–4 days): If the
ovum is not fertilized, the corpus luteum degener-
ates and the level of progesterone drops down. The
coiled endometrial arteries undergo spasm. The
blood supply to the spongy and compact layers of
the endometrium is reduced. The functional layer
undergoes necrosis and sloughs off, and there is
hemorrhage from the stumps of the endometrial
arteries. The sloughing continues until only raw
surface of the stratum basale is left.
N.B. It takes about 14 days after ovulation in breaking down the
spongy and compact layers of endometrium. Note the basal layer
of endometrium remains intact.
If the ovum is fertilized, first the corpus lu-
teum and then the placenta continue to secrete
progesterone, and the menstrual cycle remains
suspended during pregnancy.
2. Proliferative phase/follicular phase (5–14 days):
The proliferative phase coincides with the
secretion of the estrogen by the maturing follicles
of the ovary.
3. Secretory phase/luteal phase (15–25 days): The
secretory phase coincides with the secretion of pro-
gesterone by the corpus luteum.
4. Premenstrual phase (26–28 days): The females,
usually the younger ones, often complain of severe
spasmodic pain and external spotting of blood dur-
ing this phase due to ischemia of the uterine wall
following drop in the level of progesterone
hormone.
The features of different phases of menstrual cycle
are summarized in Table 2.1.
N.B. The menstrual cycle is a continuous process, and each phase
gradually passes into the next one.
Hormonal Control of Menstrual Cycle (Fig. 2.9)
The menstrual cycle is controlled by the hormonal se-
cretions of hypothalamus, adenohypophysis, and ovary
as follows (Fig. 2.9):
1. The hypothalamus secretes gonadotrophin-releas-
ing hormone (GnRH).

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 Reproductive System 17

Table 2.1 Features of different phases of the menstrual cycle

Phase
Menstrual phase (1–4 days)
Proliferative phase (5–14 days)
Secretory phase (15–25 days)
Premenstrual phase
(26–28 days)
Features
Necrosis and shedding of the functional layer of the endometrium associated with bleeding
Regeneration of the functional layer of the endometrium
Endometrium becomes thick and soft due to increased secretory activity of endometrial glands
Ischemia of endometrium due to reduced blood supply
Cramping or pain and external spotting of blood

Hypothalamus
GnRH

LH

Adenohypophysis FSH

Ovary
Progesterone
(ovarian cycle)
Estrogen

Ovulation Secretory
Uterus (uterine/ phase
menstrual cycle) Proliferative
Menstrual phase Premenstrual
phase phase

Days 0 4 8 12 14 16 20 24 28

Fig. 2.9 ​Hormonal control of the menstrual cycle.

2. The GnRH acts on the adenohypophysis, which in
turn secretes FSH and LH.
3. The FSH causes maturation of one or more ovarian
follicles. The secondary follicle is converted into
the Graafian follicle.
4. The granulosa cells of the secondary and Graafian
follicles secrete estrogen.
5. The estrogen stimulates the uterine endometrium
to enter the proliferative phase (the level of estro-
gen rises to a peak just before the LH surge).
6. The LH surge stimulates ovulation.
7. Following ovulation, the lutein cells of the corpus
luteum secretes progesterone.
8. The progesterone stimulates the uterine endome-
trium to enter the secretary phase.
N.B. The hormones secreted by hypothalamus, adenohypophysis,
and ovary prepare the endometrium of the uterus for implantation
of the conceptus (blastocyst). If fertilization does not occur, the
granulosa cells produce inhibin, a protein that acts on adenohy-
pophysis and inhibits the secretion of gonadotrophins, which leads
to the regression of corpus luteum. The endometrium undergoes
ischemic necrosis due to decreased levels of progesterone and
estrogen, especially progesterone secretion by the degenerating
corpus luteum.
For details, see Chapter 3.
The ovarian and menstrual cycles go on hand in hand
throughout the reproductive life of women, except during

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18 Textbook of Clinical Embryology

pregnancy. These cycles terminate at menopause, usually

between the ages of 45 and 55 years.
N.B. Correlation between ovarian and menstrual cycles: The
ovarian and menstrual cycles run parallel to each other. Both these
cycles are of 28-day duration.
In fact, the menstrual cycle is dependent on the ovarian cycle
because the uterine endometrium undergoes cyclic changes under
the influence of hormones secreted by the developing ovarian
follicles and corpus luteum of the ovary.
Clinical Correlation
Use of hormones in birth control (contraceptive) pills: The sex
hormone estrogen with or without progesterone is used in the
preparation of contraceptive pills. These hormones in contracep-
tive pills act on the hypothalamus and pituitary gland resulting
in inhibition of secretion of GnRH as well as FSH and LH, the
secretion of which is essential for ovulation to occur. The sup-
pression of ovulation is the basis for the contraceptive pills.
The most common variety of the contraceptive pill distrib-
uted by the government of India contains progestin (norethis-
terone acetate) 1 mg and estrogen (estradiol) 50 mg. These pills
are distributed in packets, with each packet containing 28 pills.
Of these 28 pills, 21 contain these hormones and 7 do not con-
tain hormones. The woman is asked to start taking these pills
5 days after the onset of menstruation and continue without
any break as long as pregnancy is not desired. Normal menstrua-
tion occurs during 7 days in which she takes pills without
hormone. If the contraceptive pills are taken on a regular basis,
the menstrual cycles occur regularly, each with 28 days. When
she starts taking pills without hormones after 21 days, the with-
drawal of hormone induces menstruation after 2 days.
Sperm Transport (Fig. 2.10)
During coitus (sexual intercourse) about 200–
600 million sperms are deposited around the external os
of the cervix and in the fornices of the vagina. The
following factors are responsible for passage of sperms
from the uterus to uterine tubes:
1. Muscular contractions of the walls of the uterus
and fallopian tube (main factor). The prostaglan-
dins of semen are thought to stimulate uterine
contractions during sexual intercourse.
2. Movements of the sperms: The fructose secreted by
the seminal glands provides energy to sperms.
N.B. Out of 200–600 million sperms deposited in vagina, only
about 200 sperms reach the fertilization site. Most of them degen-
erate and are absorbed by the female genital tract.
Oocyte Transport (Fig. 2.10)
During ovulation, a secondary oocyte is discharged on the
surface of ovary just before ovulation, the fimbriated
end of the fallopian tube becomes closely applied to the
surface of the ovary, and the finger-like fimbriae start
moving back and forth (sweeping action) over the
ovarian surface. The sweeping action of fimbriae and
fluid currents produced by cilia of the mucous lining of
fimbria sweeps the ovum (secondary oocyte) into the
infundibulum of the uterine tube as soon as it is dis-
charged from the ovarian follicle.

Site of fertilization

Sperm
Ampulla of uterine tube
Uterine tube
Ovum
(secondary oocyte)

Uterine
cavity
Ovary

Cervical canal

External os
Sperm

Fig. 2.10 ​Transport of sperms and ovum to the site of fertilization.

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From infundibulum, the oocyte passes to the am-
pulla of the tube mainly by the peristaltic movements
of the tubal wall.
Viability of Gametes
The female gametes (mature oocytes) generally re-
main viable for 24 hours after ovulation. They are usu-
ally fertilized 12 hours after ovulation.
GOLDEN FACTS TO REMEMBER
 Total number of seminiferous tubules in each testis
 Most important function of testis
 Reproductive period of woman’s life
 Most important event of the ovarian cycle
 Menarche
 Menopause
 Most important feature of menstrual cycle
 Most important factor to initiate menstruation
 Most common cause of amenorrhea (i.e., absence
of menstruation)
 Most precarious time of prenatal development
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Reproductive System 19
The male gametes (sperms) generally remain via-
ble for 48 hours in the female genital tract.
N.B. According to some authorities, female and male gametes
may survive up to 2 and 4 days, respectively.
400–600
(a) Formation of sperms
(b) Production of testosterone hormone
Period during which she can bear children
Ovulation
Onset of first menstruation (takes place at about
12 years of age)
Age at which menstruation ceases to occur
Monthly flow of blood per vaginum
Withdrawal of estrogen and progesterone hormones
Pregnancy
Embryonic period (3rd week to 8th week)
20 Textbook of Clinical Embryology

CLINICAL PROBLEMS

1. When an infertile (childless) couple visits a doctor, why male fertility is evaluated first?
2. What are the causes of male infertility?
3. What is the most effective permanent method of contraception in males?
4. In some women the cause of infertility is anovulation (i.e., cessation of ovulation). Is it possible to induce ovulation
in these women?
5. How is ovulation assessed clinically?
6. What is the importance of determining the time of ovulation?
7. Which is most precarious time of prenatal development (i.e., period of greatest sensitivity to teratogens)? Give
the embryological basis.

CLINICAL PROBLEM SOLUTIONS

1. This is because the semen analysis is easier to perform. The average volume of semen ejaculated in the vagina during
sexual intercourse is 2–6 mL (average 3.5 mL). There are usually more than 100 million sperms per mL of semen of
normal males. A man with less than 10 million sperms per mL of semen is likely to be sterile, especially when the
specimen contains immotile and abnormal sperms.
2. The common causes of male infertility are low sperm count (oligospermia), poor sperm motility, abnormal sperms,
and obstruction of the genital tract (e.g., vas deferens).
3. The most effective permanent method of contraception in males is vasectomy. This procedure involves the excision
of a segment of each ductus (vas) deferens. Following vasectomy, there are no sperms in the semen or ejaculate, but
the volume remains the same.
N.B. First one or two ejaculate may contain sperms.

4. In some women, ovulation does not occur due to inadequate secretion of FSH and LH. Ovulation can be induced in
such women by administrating gonadotrophins or an ovulatory agent such as clomiphene citrate. By competing
with estrogen for binding sites in the adenohypophysis, the clomiphene citrate suppresses the normal negative feed-
back loop of estrogen on the adenohypophysis. This in turn stimulates the release of pituitary gonadotrophins (FSH
and LH) secretion, which causes maturation of several ovarian follicles and thus induces ovulation.
5. Ovulation can be assessed because it is accompanied by:
(a) A variable amount of abdominal pain in some women called mittelschmerz (German 2 mittel 5 mid 1 schmerz 5
pain) because ovulation results in slight bleeding in the peritoneal cavity.
(b) A slight drop in the basal body temperature.
In a 28-day menstrual cycle, the ovulation takes place at about the middle of the cycle, to be exact on day 14 before
the start of next menstrual bleeding.
There are many methods to find out the exact time of ovulation, but the one that is easy and commonly used is the
temperature method. In this method, woman’s body temperature is recorded every morning before she gets up and
plotted on a graph. The temperature is low during menstruation, subsequently it rises, and at about the middle of the
cycle it suddenly falls to rise again. The rise in temperature after sudden fall indicates that ovulation has occurred.
Following ovulation, the basal body temperature increases by 0.3–0.5°C.

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 Reproductive System 21

6. The importance of determining the time of ovulation is twofold:

(a) Rhythm method of family planning (i.e., pregnancy is not desired): After ovulation, the ovum remains viable only
for 2 days and sperms deposited in vagina remain viable only for 4 days. Therefore, fertilization can occur only if
intercourse is done 4 days before ovulation to 2 days after the ovulation. Barring these 6 days, the remaining
days of the menstrual cycle are regarded as safe period. Thus, pregnancy can be avoided if intercourse is done
during safe period.
(b) Achievement of pregnancy (i.e., pregnancy is desired): In case of infertility (failure to conceive), the couples are
advised to have sexual intercourse during the unsafe period (i.e., 4 days before ovulation to 2 days after the
ovulation) because this period is most favorable for conception.
7. The most precarious time of prenatal development is during the embryonic period (i.e., from the beginning of the
3rd week to the end of the 8th week) because there is much tissue differentiation and organ formation during this
period. Mostly, however, a woman does not realize that she is pregnant until it is very late. Therefore, a woman should
consistently take care of herself and abstain from taking certain drugs including antibiotics (especially during
14 days before next menstruation) even if there is a remote chance that she is pregnant or might become pregnant
in the near future.

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 Cell Division
and Gametogenesis

Learning Objectives Each gamete has only 23 chromosomes. In females , all

After studying this chapter, the student should be able to:
• Define the terms mitosis and meiosis and discuss their
sign ifica nee.
• List the distinguishing features between mitosis and meiosis.
• Write short notes on spermatogenesis and oogenesis.
• Write short notes on spermiogenesis, ovulation and corpus
luteum.
• Give brief account of development of ovarian follicles and
their functional significance.
• Discuss structure of male and female gametes.
oocytes are of only one type, i.e., each oocyte contains
22 autosomes and one X chromosome (22X). In males, sperms
are of two types - one type containing 22 autosomes and 1 X
chromosome (22X) and the other type containing 22 auto-
somes and 1 Y chromosome (22Y). The sperm containing X
chromosomes is called X-bearing sperm or gynosperm and
the sperm containing Y chromosomes is called Y-bearing
sperm or androsperm.
Cell Division

Overview There are two types of cell divisions: mi tosis and

me10s1s.
The human body is made up of 60-100 trillion of cells. The body
cells are broadly divided into two types: somatic cells and germ
cells. The somatic cells undergo mitotic cell division. They are
Mitosis
essential for growth, development, regeneration, and maintenance
Th is type of cell division occurs in somatic cells. T he
of various tissues of the body, whereas germ cells undergo meiotic
mi tot ic cell d ivision is a process in which one cell
cell division. They are essential for the production of gametes.
divides into t wo daugh ter cells that are genetically
Life begins as a single cell- the zygote formed by the union
identical to the parent cell. Each daughter cell re-
of male and female gametes. In humans, the male gametes are
ceives the complete complem ent of 46 ch rom osom es.
spermatozoa or sperms, which are produced by testis from
The period between the two mitotic d ivisions is
puberty onward. The female gametes are oocytes, which are
called inte rphase. D uring interphase, i.e., before
released from ovary in a cyclic fashion throughout the repro-
m itosis beg ins, each chrom osom e replicates its deoxy-
ductive life of a female.
ri bonucleic acid (DNA). During thi s period, the ch ro-
The gametes are specialized cells for reproduction. Each
mosom es are in the form of long and thin th read s
gamete cell has a haploid (half) number of chromosomes (i.e.,
(chrom atin threads), which spread d iffusely within
23 chromosomes) . Each body cell (somatic cell) has diploid
the nucleus. These cannot be recog nized with a lig ht
(double) number of chromosomes (i.e., 46 chromosomes) . The
microscope (Fig. 3. 1).
46 chromosomes are arranged in 23 pairs. The 22 pairs of these
The various stages of mitosis are as follows (Fig. 3.2):
chromosomes are called autosomes, whereas the 23rd pair is
called sex chromosomes. The sex chromosomes are of two 1. Prophase: In thi s stage, nucleolus disappears. The
types: X and Y. Females have two X chromosomes, while males chrom osom es becom e coiled .* They condense,
have one X and one Y chromosome. Conventionally, this is
expressed as a formula 44XX in females and 44XY in males. *Shortening of chromosomes by coiling reduces the chances of p inch-
ing off of t he frag ments of ch romosomes.

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 Cell Division and Gametogenesis 23

Nucleolus Nucleolus

Nuclear Replication
membrane of DNA
Chromatin
threads
A B

Fig. 3.1 ​Cell in interphase stage: (A) early interphase; (B) late interphase.

Centriole

Spindle
fibers
Nuclear
membrane

Centromere

A B C
Prophase Prometaphase Metaphase
• Chromosome with two identical chromatids • Centrioles move to opposite poles • Nuclear membrane disappears
• Chromatids are not recognized • Chromatids become recognizable • Chromosomes line up on equator
• Are attached to the spindle fibers

Cleavage Cytokinesis
furrow

D E Formation of two daughter cells

Anaphase Telophase with same number of chromosomes
as the mother cells
• Centromere splits • Nuclear membrane reforms around
• Chromatids become daughter each polar group of chromosomes
chromosomes • Appearance of cleavage furrow in the cell
• One daughter chromosome of • Chromosomes uncoil
each pair moves to either pole • Nucleolus reappears

Fig. 3.2 ​Various stages of mitosis.

shorten, and thicken. Each chromosome now con-
sists of two parallel subunits called chromatids,
which remain joined to each other at a narrow
common region called centromere. But the chro-
matids cannot be recognized in this stage.
2. Prometaphase: In this stage, the chromatids
become distinguishable.
3. Metaphase: In this stage, the nuclear membrane
breaks. The double structured chromosomes (vide
supra) line up in the equatorial plane of the spindle
and get attached to the microtubules of the spindle
extending between two centrioles, one at each pole.
4. Anaphase: In this stage, the centromere of each
chromosome splits and the two chromatids are
separated from each other. They are now called
daughter chromosomes. The spindle fibers attached to
the centromere of the chromosomes contract and
pull the daughter chromosomes towards poles.

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24 Textbook of Clinical Embryology
Because of pull on centromere, the daughter chro-
mosomes become V-shaped with their arms trail-
ing as they move toward the poles.
5. Telophase: In this stage, the separated chromatids
are migrated to the opposite poles of the spindle.
The spindle fibers disappear and nuclear mem-
brane appears around each polar group of daughter
chromosomes. The chromosomes uncoil and
become less compact. The nucleolus reappears.
There appears a cleavage furrow beneath the equa-
tor that deepens and separates the two daughter
cells (cytokinesis).
Clinical Correlation
Significance of mitosis
1. Genetic stability: It ensures continuous succession of identi-
cal cells through generations.
2. Growth and development: It helps in growth and develop-
ment of the body.
3. Regeneration, replacement, and repair: It helps in regenera-
tion of new cells to replace the dead or damaged cells.
Meiosis (Fig. 3.3)
The meiosis is a special type of cell division that takes
place only in the germ cells to produce male and fe-
male gametes. The meiosis consists of two cell divi-
sions that take place one after the other. (a) First
meiotic division (meiosis I or reductional divi-
sion): In this division, the number of chromosomes of
the daughter cells is reduced to half of the mother
cell. (b) Second meiotic division (meiosis II): It is
the mitotic division similar to one described above
except that there is no duplication of DNA during
short interphase.
First Meiotic Division
1. Prophase: Prophase of the first meiotic division is
very long and complicated. It is therefore sub­
divided into five stages.
(a) Leptotene: In this stage, the chromosomes, as in
mitosis, appear as slender threads. Note:
Although each chromosome consists of two
chromatids that are joined at centromere, the
chromatids are not visible at this stage.
(b) Zygotene: In this stage, the lengthwise pairing
of homologous chromosomes begins. One of the
two homologous chromosomes is from the
father (paternal chromosome) and the other is
from the mother (maternal chromosome).
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This event is called synapsis and each synaps-
ing pair is called bivalent.
(c) Pachytene: This stage is very long and may
extend even for years. It is characterized by
following changes:
– The chromatids of each chromosome
become visible separately. Each bivalent
chromosome thus appears to have four
chromatids and is called tetrad. Each chro-
matid pair is united by a kinetochore.
There are two central chromatids and two
peripheral chromatids (one from each
chromosome).
– The two central chromatids (one belonging
to each chromosome) of tetrad coil over
each other so that they cross at a number
of points. This is called crossing over.
Because of crossing over, the central chro-
matids present a cross-like configuration
called chiasmata
(d) Diplotene: During this process, the paired
homologue of tetrad starts separating. The
central chromatids break at the point of cross-
ing over and unite to the opposite chromatid.
This results in exchange of genetic material
between these chromatids.
(e) Diakinesis: The chromosomes become more
contracted and migrate toward the nuclear
membrane. At the end of prophase, the nuclear
membrane disappears.
2. Metaphase: The homologous pairs of chromo-
somes become arranged on the equatorial plane of
the spindle.
3. Anaphase: In this stage, the homologous chromo-
somes migrate to the opposite poles of the spindle.
Unlike mitosis, the chromosomes move randomly.
The shorter chromosomes move earlier than the
longer chromosomes.
4. Telophase: In this stage, the nuclear membrane is
formed around the polarized group of chromo-
somes. The cell membrane constricts and two
daughter cells are formed (cytokinesis). Each
daughter cell thus formed contains only half the
number of chromosomes (haploid number) with
exchanged genetic material.
Second Meiotic Division
The second meiotic division is essentially similar
to mitosis. It, however, differs from mitosis in that
the DNA does not duplicate. In second meiotic divi-
sion, the two daughter cells of first meiotic division
form four daughter cells, each with haploid number
of chromosomes.
 Cell Division and Gametogenesis 25

Bivalent Tetrad Chiasma

A B C D E
Leptotene Zygotene Pachytene Diplotene Diakinesis
• Chromosomes appear • Pairing of homologous • Four chromatids • Crossing over • Chromosomes
as slender threads chromosomes (bivalent) become visible (synapsis of two after genetic
• Each chromosome (tetrad) central chromatids) exchange migrate
consists of two • Formation of towards the nuclear
chromatids chiasmata membrane

Praphase

• Formation of spindles
• Homologous chromosomes
get arranged on the equatorial
plane

Metaphase

• One entire chromosome migrates to

Anaphase the opposite pole
• There is no splitting of chromosome

Two daughter cells containing

Telophase
half the number of chromosomes
(haploid number)

Second meiotic division after

short interphase

Formation of four daughter cells

each with haploid number of
chromosomes

Fig. 3.3 ​Meiotic divisions I and II: (A, B, C, D, and E) showing five stages of prophase of first meiotic division.

Clinical Correlation
material during crossing over in the meiosis, the daughter
Significance of meiosis cells (i.e., gametes) have a new genetic configuration. This
1. Maintenance of normal chromosomal number: As the chro- causes individual variations within the species, which is
mosome number is reduced to half during meiosis, each germ essential for evolution.
cell has haploid number of chromosomes. When two germ cells 3. Hybrid vigor: Meiosis helps to maintain vigor in progeny
unite to form a zygote, the chromosome number is restored to through sexual reproduction.
normal (diploid number of chromosomes). Thus, because of
meiosis, the chromosome number is maintained for the species.
2. Genetic variation: Because of random assortment of pater-
nal and maternal chromosomes, and exchange of genetic The distinguishing features between mitosis and
meiosis are given in Table 3.1.

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26 Textbook of Clinical Embryology

3. Each secondary spermatocyte immediately

Table 3.1 D
 istinguishing features between mitosis
and meiosis
Mitosis
Takes place in somatic cells
Completes in one sequence
Crossing over of chroma-
tids does not take place
Daughter cells have the
same number of chromo-
somes as parent cells
Meiosis
Takes place in germ cells
Completes in two sequences,
i.e., there are two successive
divisions, namely, meiosis I
and meiosis II
Crossing over of chromatids
takes place
Daughter cells have half the
number of chromosomes as
parent cells
undergoes second meiotic division (i.e., mitotic
division) to form two spermatids, each with hap-
loid number of chromosomes.
The spermatids are small cells of about half the
size of the secondary spermatocyte, and have round
and darkly stained nuclei.
The spermatids lie close to the lumen of semi-
niferous tubule.
4. The spermatids are transformed into four mature
spermatozoa by a process called spermiogenesis.
N.B. One primary spermatocyte forms four spermatozoa; two
containing X chromosomes and two containing Y chromosomes
(Fig. 3.4)

Daughter cells are identical
to each other and to the
parent cell
Equational division
Daughter cells are not
identical to each other and to
the parent cell
Reductional division
The steps of spermatogenesis are summarized in
Flowchart 3.1.
To understand the process of spermiogenesis, the
student must first understand the structure of sperma-
tozoon (Fig. 3.5).

Structure of Spermatozoon (Fig. 3.5)

Spermatogenesis (Fig. 3.4)
The spermatozoon (50 microns in length) consists of
The spermatogenesis is process of formation of sperma- head, neck, and tail. The tail is further divided into
tozoa from spermatogonia. The spermatogonia are de- three parts: middle piece, principle piece, and end
rived from primordial germ cells by a process called piece. Tail forms four-fifth of the length.
spermatocytogenesis (Fig. 3.4 in the inset).
The primordial germ cells (PGCs) are present in the
wall of the seminiferous tubules of the testis.
They remain dormant in the seminiferous tubules
Primordial germ cell
of testes till puberty. At puberty (12–16 years), these
SPERMATOCYTOGENESIS
cells undergo a series of divisions to form spermatogo-
nia. They start forming gametes, i.e., spermatozoa Spermatogonium (Type B)
and this continues throughout the reproductive life of Mitosis
a male, i.e., up to old age.
The PGCs divide by mitosis to form dark type A Primary spermatocyte
(44XY, 4nDNA)
spermatogonia, which act as stem cells. Each dark type
A spermatogonium undergoes mitosis to form one First Meiotic Division
dark type A spermatogonium and other light type A Secondary spermatocyte
spermatogonium. The dark type A spermatogonia are (22X/Y, 2nDNA)
kept in reserve for repetition of the next cycle. The Second Meiotic Division
light type A undergoes mitotic division to form two
Spermatid
dark type B spermatogonia. (22X/Y, nDNA)
The sequence of events by which spermatogo-
nia are transformed into spermatozoa as follows:
Spermatid
1. The type B spermatogonium undergoes mitotic (22X/Y, nDNA)
division to form two primary spermatocytes
SPERMIOGENESIS
(largest germ cells).
2. The primary spermatocytes undergo first meiotic Spermatozoon
(22X/Y, nDNA)
division (reductional division) to form two secondary
spermatocytes. The secondary spermatocytes thus
Flowchart 3.1 ​Steps of spermatogenesis.
have haploid number of chromosomes.

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 PGC
Primordial
44XY
germ cell (PGC)
44XY
Mitosis

Dark type A Dark type A

spermatogonium 44XY 44XY spermatogonium
Spermatogonium
44XY
(Type B)

Light type A Dark type A

Mitosis Primary 44XY 44XY spermatogonium
spermatogonium
spermatocyte
(largest
First meiotic 44XY germ cell) Type B Type B
division spermatogonium 44XY 44XY spermatogonium

22X Secondary 22Y

spermatocytes
Second meiotic
Second meiotic
division
division

22X 22X Spermatids 22Y 22Y

Spermiogenesis

Cell Division and Gametogenesis

Spermatozoa

22X 22X 22Y 22Y

Fig. 3.4 ​Spermatogenesis. Figure in the inset on the right shows spermatocytogenesis.

27
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28 Textbook of Clinical Embryology

Parts of sperm Structure of different parts of sperm

Cell membrane
Acrosomal cap

Head Nucleus

Cell membrane
Neck Basal plate
Proximal centriole
Middle
piece Cell membrane
Mitochondrial sheath

Nine outer dense fibers

Axial filament (cilium
with 9+2 arrangement)

Tail Principal
Cell membrane
piece
Fibrous sheath
Seven outer dense fibers
Axial filament

End Cell membrane

piece Axial filament

Fig. 3.5 ​Human sperm. The parts of mature sperm are shown on the left side, whereas the sections through the head, neck,
middle piece, principal piece, and end piece along with their composition are shown on the right side.

Head The head of sperm appears somewhat like a 3. End piece: It is made up of only the axial filament.
spearhead in section. It mainly consists of a nucleus
N.B.
that contains the condensed chromatin material (mostly l Structure of the axial filament is very similar to that of the

DNA). Anterior two-third of the nucleus is covered by cilium.

an acrosomal cap that contains various enzymes l The whole spermatozoon is covered by plasma membrane.

including hyaluronidase and acrosin.

Fig. 3.5 shows parts of the mature sperm (on the
Neck The neck is narrow. It contains a funnel-shaped left) and sections through head, neck, middle piece,
basal plate and a centriole. The centriole gives rise to principal piece, and end piece along with their compo-
axial filament that extends throughout the tail. sition (on the right).

Tail The tail consists of three parts: middle piece, N.B. The axial filament is responsible for the movements of the
spermatozoon, while mitochondria supply energy for these
principal piece, and end piece. movements.

1. Middle piece: It contains the axial filament in

the center, which is surrounded by spirally
arranged mitochondrial sheath. At the distal
end of the middle piece there is a ring-like struc-
ture through which axial filament passes. It is
called annulus and is derived from the other
centriole.
2. Principle piece: It is made of axial filament
covered by seven outer dense fibers.
Spermiogenesis
The process by which the spermatids are transformed
into mature spermatozoa is known as spermiogenesis.
Process of Spermiogenesis (Fig. 3.6)
The spermatid is more or less a circular cell contain-
ing a nucleus, Golgi apparatus, centrosome, and

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 Yet of all the pictures of either the stately or the modest homes of
Scotland, which now hang in the gallery of memory, none exceeds in
beauty and charm those of the home at Invergowrie, where we were
several times guests. Here was a typical Scottish family of character
and culture. Father and mother were in the prime of life, health, and
manifold activities. Around them had grown up a family of sons and
daughters, from the youngest, a blooming maiden of eighteen,
educated in Germany and at Brussels, to the eldest son, who,
besides being active in business, was an officer in the local volunteer
artillery corps. At night he loved to put on his Highland suit for
comfort and enjoyment, as we chatted with his friends on British and
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after President Cleveland had issued his strenuous proclamation
concerning Venezuela, when British feelings were hurt and when a
combination of tact, some knowledge of history, and of the political
and personal motives of American Presidents was necessary to the
guest and peacemaker.
The Invergowrie family honored the American in Scotland more
than once by inviting, to the dinners given in his honor, the
professional gentlemen of the neighborhood and from Dundee.
While in Scotland one must beware of what toes he is likely to
tread upon, should he nurse opinions differing from those welcomed
by people holding any of the various shades of Presbyterianism,
whom he will probably meet anywhere and everywhere. It was in
Scotland, above every other country, that we learned what it meant
to “mind your p’s,” yet our hope is that we succeeded measurably.
The garden parties, in which the young people had their fun and
amusement, the five o’clock teas, at which the ladies of the
neighborhood dropped in for chat and friendly calls, were as
delightful to enjoy as they are now pleasant to recall. Yet, as in the
United States the county fair excels all other inventions and facilities
for seeing the real, average American, so I valued most, for intimate
knowledge of the Scottish populace of all grades and ages, the local
exhibitions, “bazaars,” and gatherings.
To be present, as we often were, to see the modern version of
“The Cotter’s Saturday Night,”—though in this version we mean a
luxurious home, with all the appointments of comfort, culture, and of
service,—crowned all delights. This social situation in Scotland is
necessarily different from that in America, where, in the cities at
least, native-born maidens so rarely take domestic service in
families. With our composite people, also, there is usually such a
disagreement as to the theories of the universe, as taught by priest,
parson, and rabbi, that worship of the same God by all, at one time,
in the same way, and in one household, seems impossible. The
head of the house or the mistress holds usually to one form of
dogma or ritual, while the servants have been reared in an
atmosphere so very different that family worship, with the “help”
joining in or present, is, to say the least, not customary in “the land of
the free.” Occasionally British visitors, who imagine that the very
mixed people called Americans are descended chiefly from insular
instead of continental stock, like the late James Anthony Froude
when in New York city, for instance, make disagreeable discoveries.
At times, in our democracy the kitchen rules the parlor.
At Invergowrie, as in a score or more of homes on the island in
which I have been so often a guest, the two or three maids and
perhaps a man-servant came in with their Bibles and read, with the
children of the household, the Word which is above every other word
—the Father’s message to his children. Where there was but one
servant, the same rule usually held. At Invergowrie, besides a
chapter of Scripture and a prayer by the father, the high priest of the
family, the older son read one of the Psalms in Rous’s metrical
version.
The breakfast in Scotland, as in the British Isles generally, is one
that suits admirably the free-born Briton. It is certainly a festival of
freedom for the servants, who are usually apt to be upstairs or
attending to other domestic duties, though in a large family, the
members of which sit down at the same time, there is usually one
maid present to wait upon the table. At several places where I was
entertained, even in well-to-do families, the grown sons and
daughters or members of the household came and went at their
convenience, helping themselves at will from dishes on a sideboard.
After the table has been laid by one of the maids, who may or may
not remain present, it may be that the elder daughter serves. At
Invergowrie there was a large, normal family, consisting of parents
and children, with sufficient uniformity of dispositions and habits to
make both the breakfast and the dinner time a delightful gathering,
with merriment and leisure. The news of the day, the happenings of
the neighborhood, the things alike and different as between Scotland
and America, the annals of the village fair, or the social chat, or
those pleasant nothings that lubricate life, made the moments pass
all too rapidly.
That father benign and mother of imposing presence have been
long laid to sleep; but in London, and Edinburgh, and Dundee, in the
world at large, live yet these sons and daughters of “Bonnie
Scotland” who have made the Americans’ memories of their lovely
home in their home land a storehouse of delight.
Besides the private grounds of the home, with their trees and
shrubbery, there were walks that afforded plenty of room for rambles.
Still farther afield, yet not far away from either the house or the
railway station, were ruins of Dargie Church. These touched the
imagination and called history to resurrection. It appeared strange to
come across the footprints of our old friend St. Winifred, or Boniface,
whom we met with in our studies of the Pilgrim Fathers, and in the
Netherlands, whose varied and strenuous life, as ecclesiastical
politician as well as saint and soldier of the Papacy, quite as much
as preacher of the gospel, was one of such amazing activity. At
Scrooby in England, at Dokkum in Friesland, in France and in
Germany, where I visited the places made historic by his activities,
he left enduring marks of his influence and power.
At Invergowrie I meditated among the ruins of the old kirk, in
which, or near by, it is said, St. Boniface, the apostle to Germany
and a legate from the Church of Rome, in the eighth century
preached and planned to neutralize the work of the Irish monks in
favor of British uniformity, and by means of conformity with Rome.
Here also are still to be seen some singular examples of ancient
sculptured stone monuments.
 In 1107, Alexander I, son of Margaret of England, had a
residence at Invergowrie, which, however, he did not long possess,
for assassination was so much of a pastime with many and a settled
custom with a few in those days, that, after having escaped the dirk
only by a narrow margin, he left Invergowrie, built a church at Scone,
and then turned over the property he left behind him for its support.
I recall that it was at the last of our visits and entertainment at
Invergowrie, which was in 1900, after the ladies had left the dinner
table and the gentlemen adjourned to the billiard-room for a smoke,
the conversation turned on the next European war, and the possible
relations of Great Britain and the United States in the alignment of
friends, foes, allies, and neutrals. One prominent Dundeean
confessed himself not so much exasperated, as hurt, by President
Cleveland’s sharp method of reasserting the Monroe Doctrine, in
regard to the boundary of Venezuela. From our town of Ithaca, the
two scholars, the ex-president of Cornell University and Professor
George Burr, had been summoned to consult archives, rectify
boundaries, and help keep the peace. After the American in Scotland
had emptied his cruse of oil upon the waters, by explaining some of
the ins and outs of American politics, the conversation drifted to
regions across the North Sea—the growth of the Kaiser’s navy, the
salient features of German politics, and the reports, then very direct
from the Fatherland, that the “Kultur” of the twentieth century
required that “England [Great Britain] needed to be taught a lesson.”
The hope was warmly expressed that, in the coming clash,—then
looked for to come before many years,—the sympathy, and even aid,
if necessary, of “the States” would be forthcoming. With American
friendliness and the possession of the coaling-stations of the world, it
was believed that the United Kingdom could withstand the coming
shock and recover triumphantly.
More than once, at these social conferences with Scotsmen, as
well as in the press, I noted the indignation, even anger, expressed,
that in all national affairs it was “England” and “the English” that took
and received the credit for what belonged to the four nations making
up the United Kingdom. The claim was for a more liberal use of
“Britain” and “British” in place of “England” and “English.” Both
Scotch and Irish, to say nothing of the Welsh, resent the assumption
that “England” is the British Empire. In a word, the great need of the
language used in the British archipelago is a common name for the
federated four countries and for all the subjects of the Crown. Here is
an instance of the priceless value of right words. The absence of an
acceptable comprehensive term is a real impediment to patriotism
and an obstacle to perfect union. The fault is in language, not in the
human spirit. The situation reinforces the argument that “words are
things.”
We Americans can throw no stones. Canadians, Mexicans, the
southern republics below Panama, all challenge our right to the
monopoly of “America” and “Americans.” Language lags behind
events.
When at last, in 1914, the great war did come, and the storm
broke, no part of the Empire responded more quickly, generously,
fully than Scotland, nor did any courage or sacrifice exceed that of
the Scots; yet, not only was the credit usually given to “England,” but
even the prayer of hate, made in Germany, chose “England” as its
butt. Yet while Scottish valor and sacrifice and Irish courage and
free-will offerings of life on the field and waves are unstinted, who
can blame the poet, nay, who does not say “amen,” to his lines, in
the Glasgow “Herald,” written in the closing days of 1915?

“The ‘English’ navy in its might

Is out upon the main;
The ‘English’ army—some in kilts—
Is at the front again;
The dogs of war are loosened
And gathering to the fray,
But the British ships and British troops—
I wonder where are they?
 “When blood has flowed like water,
And ’midst the heaps of slain
Lie stalwart Scot and brawny Celt
Who victory help to gain,
The glory will be ‘England’s,’
Like every other thing;
’Tis ‘England’ this and ‘England’ that—
Flag, navy, army, king.

“Still let Scots do their duty

In Britain’s day of war;
A greater cause than ‘England’s’
Nerves Scottish hearts by far.
For Britain and the empire
We Scotsmen draw the sword,
And not like hired mercenaries,
As if ‘England’ were our lord.”

During this trial of the soul of a nation, in the wager of battle, to

decide whether truth is worth living and dying for and whether
solemn compacts are as torn paper—we catch a glimpse of a great
part of the nation at prayer.
It is in St. Giles’s Church, Edinburgh, that the General Assembly
of the Church of Scotland holds its annual sessions and the function
is made decidedly spectacular, as is supposed to become a State
Church. For two hundred and twenty-five years, the meeting has
been held without interruption. In the brilliant procession, the Lord
High Chancellor, as representative of the king, takes part, and
usually a regiment of the garrison troops adds color and a show of
worldly might to the spectacle. Few elements appropriate to the day
are omitted, for this is the august assembly of the “Church
established by law.” In the spring of 1914, the full strength of the
Cameron Highlanders was paraded.
 FOR THE WHOLE WORLD
(The Edinburgh Conference of Missions)
But in 1915, after the gates of hell had been fully opened on the
Continent, swallowing up, it is said, from one regiment, by death and
wounds, no fewer than nine hundred of the Cameron Highlanders,
leaving but one hundred unwounded survivors, the meeting was
more than usual like a gathering of the ministers of the Prince of
Peace. The king’s representative on this occasion, the Earl of
Aberdeen, was dressed in a soldier’s service uniform of khaki and
the military escort as guard of honor was a corps of cadets. The
interior phenomena were equally impressive. Men cared little for
debate and turned constantly to prayer and intercession. The high-
water mark of interest in the proceedings was on Foreign Mission
Day. Then a strong note of optimism appeared regarding that work,
in comparison with the depression felt as to other interests of the
Church. It was in Edinburgh that the world-wide conference upon
missions was held in 1913, whose influence is still felt throughout the
whole earth.
Perhaps some thoughts turned to the words of the Almighty to
Job, “And the Lord turned the captivity of Job, when he prayed for
his friends.”
Be this as it may, can we not all abide in hope that the ultimate
history of “Bonnie Scotland” will follow that of Job—“Also the Lord
gave Job twice as much as he had before.”
 CHAPTER XXV
AMERICA’S DEBT TO SCOTLAND

It is a tradition, rather than a fact, that we Americans—not of

Canada—of the United States of America are an English people.
The burden of popular and uncritical historiography is responsible for
this notion. Because of the overpowering influence of law and
language, and because our most direct relations, in war and in
peace, have been with Great Britain, it is assumed that we are both
an English people and an English nation.
The result has been confusion at home, prolonged
misunderstanding in Europe, and injustice to those who have
contributed generously their blood and energies to the making and
the saving of the nation.
Without the initial and formative elements, now absorbed into our
national composite, from the Dutch, Huguenot, German, Scottish,
Welsh, Irish, and Iroquois, the existence and history of the United
States are, to the unprejudiced mind, inconceivable. In this chapter
we propose to glance at the debt we owe to Scotland.
In point of time, in the unshackling of the human spirit, and in the
attainment of mental and spiritual freedom, we have shown how
Scotland led Europe; first in revolt against kings and prelates, and
then in the initiative of the constructive principles of democracy. The
spirit of Scottish history, of which Robert Burns’s poem, “A man’s a
man for a’ that,” is the epitome, and the general education of the
common people do in themselves alone show how different were
and are the Scottish from the English people.
This early Scottish influence, conveyed through both theory and
example, was especially potent with the founders of New England,
the Puritans in Old England, and the Pilgrims who, in the Dutch
Republic, received tremendous reinforcement.
In philosophy—which is greater than armies or navies—to no
other land or people were the beginners of the American nation more
indebted than to the Scotch. This may be said, not only in the
departments of political and ecclesiastical science, but equally so in
the domain of pure thought. The Scottish philosophy of realism and
common sense dominated largely our infant colleges. It swayed the
thinking and shaped the conduct of our public men in bar and pulpit.
It was translated into action by the leaders of the Revolution.
So long as the Scots were able to hold their own against the
tyrannical Stuart kings of England, and even while they were pouring
by the tens of thousands into Ulster, making a new nation in northern
Ireland,—the old land of the Scots,—there were but few emigrants,
from Scotland direct, to the Atlantic Coast colonies. Even these were
sporadic and mostly by way of Holland; but when the oppressive
economic measures of Parliament ruined the Scotch-Irish industries,
there began an emigration of people of Scottish birth or descent
which numerically excelled any previous colonial accession to
America.
Whereas, the emigration from England to New England, mostly
between 1630 and 1650, had added but twenty thousand souls to
the northeastern seacoast region, the Scotch-Irish migration, lasting
fifty years, added fifty thousand hardy, intelligent, thrifty people who
settled in the interior and on the frontiers. They not only served as a
barrier against the savages, but they developed the soil of the
valleys and built their towns on the highlands and the watersheds.
After the accession of the Hanoverian dynasty and the breaking-
up of the old economic and social conditions in Scotland, there
poured into America a flood of Scottish islanders, Lowlanders, and
Highlanders from Scotland direct, numbering tens of thousands.
From this multitude of the Scots and Scotch-Irish, scattering widely
and settling mostly on the frontiers and developing virgin land, came
forth, at the call of the Continental Congress, one third of the
American army of freedom in the Revolution.
 Throughout our history none have excelled these lovers of
ordered freedom in safeguarding human rights and in illustrating
loyalty to moral convictions and public duty. The number of able men
of Scottish descent who have filled the highest offices of honor and
trust in the learned professions, in pulpit, bar, bench, in chairs of
science, or as governors, presidents, officers of the army and navy,
and in every line of human achievement, is not excelled, if equalled,
by those of any other stock in the American blend of nationalities.
Yet the total value of such an addition to the resources of
manhood, for the making of the future American commonwealth,
cannot be estimated in mathematics only. In education almost every
classical school and colonial college in the South was established by
these people. In character and abilities—trained and nourished by
education, morals, and religion—the Scotch-Irish were excelled by
no other people.
In our land—new birth of the ages—the names of the clans and
of individuals who bear Caledonian names do not only call up
scenes in Scotland’s history, but do forcibly emphasize our blessings
of peace after long strife. One of the earliest Scottish stories I
remember was of a Grant and a Macpherson, who met one day
upon a log spanning a chasm. As neither would give way to the
other, their dirks settled the controversy by subtracting two from the
population of the Highlands. In our soldier days, it was delightful to
see, under the same flag and battling for the same Union, two
generals—the ever-victorious James Macpherson and
“Unconditional Surrender” Grant. Was it the Inverness-born
Macpherson, or the Kentuckian MacClernand, who uttered the
prophecy concerning the then closed Mississippi Valley, that “the
men of the West would, with their swords, hew their way to the
Gulf”? In any event, what would the North have done had all the men
of Scottish descent been subtracted from the hosts under Grant?
Indeed, what would American history and the reality of to-day be if all
the Scotsmen who took part were eliminated from the story? Even in
Civil War days it was largely the descendants of Scots who made the
Union sentiment in East Tennessee and created West Virginia.
 The long discipline of the Scotsmen, resulting in the gifts and
graces of Highlander, Lowlander, and Ulsterman, helped grandly on
American soil to make the great Republic possible. As we have
seen, the tens of thousands of Scots, emigrating beyond the Atlantic,
located themselves largely along the line and at the post of danger—
among the mountains they loved, on the frontier and the great
American highlands, the Appalachian chain, from Maine to Alabama.
In the infant days of our nation, when the vital struggle was between
savagery and civilization, the Scottish-American frontiersman, alert,
brave, tenacious, was the man for the era. He would never say “die”
nor give up, while life remained in him. His record, both with the
Continentals, in the War of Independence, and in the Union army
during the conflict between the States, is a shining one. In the
Confederate forces, from 1861 to 1865, the one body of men,
selected by that best judge of humanity, Professor N. S. Shaler, of
Harvard, as embodying the finer human qualities that shine brightest
in adversity, was a regiment composed almost wholly of
descendants of men of Scottish stock.
Even to hear casually some of these Scottish names, so
interesting to us in history, sets ringing the bells of memory, as when
Joseph Henry, at Albany, first sent a thrill through miles of wire to
make sound—which Morse, without electrical research or profound
knowledge, turned into writing, and thus won the world’s glory. Even
the commonplace names of neighbors, as our Scottish hosts in
Dundee, Invergowrie, or Newport-on-Tay mentioned them offhand,
set our imagination on the dance or to rambling to the ends of the
earth.
At home, too, do we not meet at school, in business, at garden
parties, or in church, girls and boys, friends and acquaintances, or
do we not hear of or see eminent men and women who bear these
their ancestral names most modestly? Immediately, a carillon of
associations, usually sweet, with “auld lang syne” sounds, fills the
secret chambers of memory. “Cochrane” may bring up a rosy face
and the laughing eyes of a pretty Vassar girl; “Macfarland” limns in
imagination a schoolmate or army comrade; “Cameron” pictures a
fellow of infinite wit; “MacIntosh” suggests eloquence in the pulpit.
Others recall the halls of Congress, or the seats of executives, or the
council board, business experiences, or clerical scenes, or pageants.
It has the sensation almost of a shower bath, or crash towel friction,
to see in court or pulpit, at clinic, or amid scenes of gentleness,
people who bear ancestral names of once slashing swordsmen, or
fellows of old famous for lifting cattle, or for defying the king’s writ, of
whom we have read often in poetry and romance. How the centuries
soften sharp outlines in the enchantment of distance!
It is invidious, if not mildly dangerous, to single out names. Yet
with one we close our sketch of “Bonnie Scotland,” choosing for
praise the dead, with no living line of descendants. Hepburn, for
example, instead of being associated in our minds with dirks and
poison, caste squabbles, or pitched battles,—after which “the turf
looked red,”—calls up the mild face of a saintly soul who illustrated
the Scripture promise of long life because of lips that refrained from
speaking guile and of hands that ever healed. Who that is at home in
Scottish history but has not infrequently run across the name of
Hepburn—which reproduces in its vocables, not only a Scottish
streamlet, but a line of mighty men? Who, also, that knows the story
of the making of modern Japan but has heard of the beloved
physician of Yokohama, known among the native-born as Kun-shi—
the sage, super-man, gentleman by eminence, who spent his life in
unselfish devotion to his fellow men, as a Christian healer, scholar,
lexicographer, and philanthropist. In the midst of fame and fortune
won by medical practice in the metropolitan city of New York, James
Curtis Hepburn turned his back on these, to uplift in body and spirit
the people of Japan, when just opened from hermitage to modern
life. In the days of sailing ships and at the seaport where the
selvages of two civilizations met, I saw him, day by day for years,
with his healing touch dispensing medicine and cheer. He lived to
make the dictionary which bridged the linguistic gulf between Orient
and Occident, to translate the Eternal Word, to raise up hundreds of
effective physicians, and, at ninety, to be honored by His Imperial
Majesty the Mikado with a decoration, and to live, in serene old age,
a benediction to his neighbors, until within five years of a century. In
him I saw America honored and the nobler Scotland incarnated.
THE END
CHRONOLOGICAL FRAMEWORK OF
SCOTLAND’S HISTORY

PREHISTORIC
Britain, “north of the Tweed.” Picts and various
tribes.

THE ROMAN PERIOD

b.c.
55. Julius Cæsar lands in southern Britain.
a.d.
50. Romans in Britain learn of the Caledonii in the
north.
81. Agricola’s frontier between the Firths of Forth
and Clyde.
82. The Ninth Legion at the Tay River.
84. Great battle between the Romans and northern
natives.
84. Caledonia circumnavigated.
120. Hadrian erects the Roman Wall.
139. Wall of Antoninus Pius.
181. Revolt of the Tribes. Commodus.
208. Uprising of the Tribes. Severus.
210. Roman road made through the Forth Forests.
364. Highland host invades the South.
368. Roman slaughter of the “Scots” (Irish invaders).
406. Revolt of the northern tribes.
410. The Romans leave Britain.
PERIOD OF ANARCHY—FIFTH TO SEVENTH
CENTURY
Migration of the “Scots” (Irish) to the peninsula.
Fergus, first “Scots” Prince.
Entrance of the Germanic, Continental tribes
into Britain.
Four kingdoms: Pictish (Pictland); Irish
(Dalriada); Brython (Strathclyde); and
“English” (Benicia).

CHRISTIAN SCOTLAND
563. St. Columba (521–592), Christian missionary at
Iona.
573. St. Kentigern at Glasgow.
651. St. Cuthbert at Melrose.
710. The Pict Christians conform to the Roman
Church rules.
717. The Columba monks expelled.
730–761. The Pict, Angus MacFergus, paramount.
802. Iona burnt by the Norsemen. Desolate for two
hundred years.
802–839. The Scandinavian sea-rovers settle on the
northern coasts.
844–860. Kenneth MacAlpine, King of the Picts.
Blending of the Picts and Scots into one people.
904. St. Andrews: religious centre. Stone of Scone.
945. Malcolm acquires northern Strathclyde.
1018. Lothian part of the Celto-Pict realm.
1005–1034. King Malcolm II.

FEUDAL SCOTLAND
1039–1056. Macbeth flourishes.
Ireland, “the Land of the Scots,” is known by its
modern name. “Scotland” refers to northern
Britain.
 1057. Macbeth defeated and slain by Malcolm
Canmore.
1066. Normans invade England.
1058–1093. Malcolm Canmore and Queen Margaret.
Great social and political changes in Scotland.
The Celtic Church gives way to Western
uniformity.
Dunfermline, capital of the realm.
1124. Alexander, King of Scotland.
Planting of Norman, Flemish, and Anglican
colonies on east coast.
Anglo-Norman feudalism in Scotland.
David I, “The Maker of Scotland,” builder of
abbeys and bishoprics.
1153–1165. Malcolm the Maiden. Great Clan of Macdonalds
formed.
Ascendancy of Anglican influence. Inverness
granted a royal charter.
1165–1214. William the Lion. Dundee granted a royal
charter.
Chimneys introduced into Scotland.
1249–1286. Alexander III. Treaty with Norway.
Islands incorporated in the Scottish realm.
1292. John Baliol crowned on the Stone of Scone.

FIVE HUNDRED YEARS OF HOSTILITY TO

ENGLAND
AND FRIENDSHIP WITH FRANCE
1297–1305. Edward of England. Intervention in Scotland.
1298. William Wallace.
1274–1329. Robert the Bruce.
1334–1346. Battle of Bannockburn.
Scotland independent.
Scottish Parliament at Cambuskenneth.
1333–1361. Struggle with Edward III of England.
King David in Captivity. Ransom. Scheme of
Union.
Struggles between Scottish kings and nobles
looking to centralization of royal power.
Partisan warfare. The House of Douglas.
1364. Proposal of Union with England rejected by the
Scottish Parliament.

THE SCOTTISH KINGS

1371–1390. Robert II. The Stuart line of kings founded.
Policy of Scotland shaped by Earls Douglas,
Mar, March, and Moray.
English invasions of Scotland.
1390–1406. Robert III. Beginning of nearly two centuries of
royal minority, regencies, and nobles’ power.
Decline of kingly authority. Great power of the
nobles.
1395. The Lollards in Scotland: forerunners of the
Reformation.
1406–1437. James I. His reign a struggle against anarchy.
Attempts to Anglicize Scotland.
Parliament of Highlanders at Inverness. Several
chiefs seized and executed.
1437–1460. James II marries Mary of Gelderland: kills
Douglas at Stirling. Earls still powerful.

THE RENAISSANCE
1460–1488. James III marries Anne of Denmark.
The thistle, the national badge of Scotland.
Witchcraft. King imprisoned by the nobles and
assassinated.
1465–1536. Hector Boece writes the “History of Scotland.”
1488–1513. James IV. Modern History of Scotland begins.
1494. Grey Friars’ Church in Edinburgh built.
 Ayala, Spanish envoy and writer on Scotland.
Music and poetry cultivated.
1495. University of Aberdeen founded.
1496. Parliament decrees compulsory education.
University of St. Andrews. Hepburn founds St.
Leonard’s College.
1503. Marriage of James IV with Margaret of England,
at Holyrood.
First Peace with England since 1332. An era of
prosperity.
1505. Royal College of Surgeons founded at
Edinburgh.
1507. Printing introduced into Scotland.
1513. Battle of Flodden Field.

THE REFORMATION
Rise of the burgesses and middle classes.
1513–1542. James V: minority. Angus rules. James escapes
to France.
1537. James marries Mary of Guise, and on her
decease, Mary of Lorraine.
1540. Lordship of the Isles annexed to the Crown.
1542. Invasion of Scotland by Henry VIII.
King and clergy on the Roman, nobles on the
Reformed, side.
1542–1587. Mary Stuart, Queen of Scots.
Close relations with France.
1505–1572. John Knox.
Destruction of monasteries and abbeys.
1557. Last Protestant martyr burned.
1565. Queen Mary marries Lord Darnley.
1566. Murder of Rizzio in Holyrood.
1567. Murder of Lord Darnley.
Marriage of Mary with Bothwell.
1567–1625. George Buchanan, scholar, reformer, author of
 De Jure Regni apud Scotos.
James VI educated by George Buchanan.

PRESBYTERIAN SCOTLAND
1560. Foundation of the National Church.
First General Assembly of Scotland.
1578. Andrew Melville the Reformer. Second Book of
Discipline.
Divine Right of Presbytery taught. Nobles
debarred from spoiling the Church.
1587. Execution of Mary Queen of Scots.
1592. James gives Presbyterianism his sanction.
1603. Union of the crowns of England and Scotland.
James VI of Scotland becomes James I of
England.
1605. The Border region pacified and civilized.
1606. The Union Jack flag, uniting crosses of St.
George and St. Andrew.

STRUGGLE FOR FREEDOM OF

CONSCIENCE
1584–1688. Scotland’s fight against prelacy.
1610. King James changes his mind. Attempts
assimilation of Church of Scotland with the
Anglican Establishment.
1618. The Perth Synod accepts episcopacy.
1600–1649. Charles I asserts the royal prerogative.
1625. Attempts to fasten the liturgy and bishops upon
Scotland.
1637. Jenny Geddes. Uproar in St. Giles’s Cathedral.
Signing of the National Covenant.
1638. Episcopacy cast out.
1645. Covenanters compel Charles I to sign the
Covenant.
1649. Charles Stuart, King of England, executed.