The reproductive System

Dr .kedir.N

April,2021
1
Aims of Life
 
 
a. Maintenance of the species
 
b. Maintenance of the individual

2
Reproduction

Significance:
 
  a. Procreation: maintenance of the species
 
b. Recreational and Relational
 
Types
 
A. Asexual
 
Binary fission  Single-celled Organisms
Vegetative propagation  Plants
Budding  Hydra, sponges, sea anemones
Parthenogenesis  Lizards
 
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B. Sexual
 
a. Genetic diversity
 Fertilization: combines genes from 2 separate individuals

b. DNA back-up and repair:

2 sets of chromosomes, recombination

Is Sex an Absolute Necessity for Procreation???

4
By the year 2025 sex will be...
 
 
1. No more procreational
 
a. In vitro fertilization  will be global
 
Nowadays in USA: >100,000 test tube babies!

b. Cloning will be legal...

 
2. Recreational + relational...
 
Sex will be for pleasure...
 
 
 
(Time: Special issue, BEYOND 2000; Nov 8, 1999 )

5
 Sex Determination

 Sex is determined by genetic inheritance of two chromosomes called the

sex chromosomes.
 
 The larger - X chromosome and the smaller, the Y chromosome.
 
 Males - one X and one Y, whereas females - two X chromosomes.

 Thus, the genetic difference between male and female is simply the
difference in one chromosome.
 
Sex distribution of the population
 Why approximately equal sex distribution of the population ?

6
 The ovum can contribute only an X chromosome; whereas half of the
sperm produced during meiosis are X and half are Y.

When the sperm and the egg join, 50% should have XX and 50 % XY.

sex ratios at birth are not exactly 1:1; rather, for unclear reasons,

there tends to be a slight preponderance of male births

7
 An easy method exists for determining whether a person’s cells contain

two X chromosomes, the normal female pattern.

 
 When two X chromosomes are present,

only one functions and the nonfunctional X chromosome condenses

to form a nuclear mass termed the sex chromatin

which is readily observable with a light microscope

(scrapings from the cheek mucosa are a convenient source of cells to be

examined)

 The single X chromosome in male cells rarely condenses to form sex

chromatin.
8
 
 A more exacting technique for determining sex chromosome composition

tissue culture visualization of all the chromosomes —a karyotype

 
 This technique has revealed a group of genetic sex abnormalities

characterized by unusual chromosomal combinations as XXX, XXY,

X, and others
 
 The end result of such combinations is usually the failure of normal
anatomical and functional sexual development

9
Sex
 
1. Chromosomal Sex/Genetic sex = Nuclear sex

a. Presence of XX or XY state of chromosome at the time of

fertilization

b. Genotype of the fertilizing sperm cell  chromosomal sex of the

fertilized zygote.

XX  Female
XY  Male

2. Gonadal Sex
a. Determined by chromosomal sex.
b. Differentiation of the primary gonad into Testis/ ovary  gonadal sex
 
10
3. Genital / = Phenotypic Sex
 
a. It is hormonally determined

b. The male is an induced sex whereas the female is a default sex

 
4. Psychological Sex
 
a. Apparent genital sex at birth  Legal sex  psychosexual
identification  sense of oneself as male or female
 
b. Sexual-orientation: dress and hair style, toilet habits...
 
c. Gender role: Biological + Psychological + Sociological factors

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12
Sex Differentiation

 It is not surprising that people with abnormal genetic endowment

manifest abnormal sexual development,

but individuals with normal chromosomal combinations but

abnormal sexual appearance and function.
 
 In these people, sex differentiation has been abnormal, and their
appearance may even be at odds with their genetic sex

—that is, the presence of XX or XY chromosomes.

 
 It will be important to bear in mind during the following description one
essential generalization:

 The genes directly determine only whether the individual will have
testes or ovaries.
 
 All the rest of sex differentiation depends upon the presence or
absence of substances produced by the genetically determined gonads

Specifically the testes 13

Differentiation of the Gonads

 The male and female gonads derive embryologically from the same site

—an area called the urogenital ridge

 
 Until the sixth week of uterine life, there is no differentiation of this
site.

 In the genetic male, the testes begin to develop during the seventh
week.

 A single gene on Y chromosome (SRY gene, for sex-determining region

of the Y chromosome)

is expressed at this time in the urogenital ridge cells and triggers

this development
 
 In the absence of a Y chromosome and, hence, SRY gene, testes do not
develop; instead, ovaries begin to develop in the same area at 11 weeks
14
 By what mechanism does the SRY gene induce formation of the testes?

 This gene codes for a protein, SRY, which acts as a transcription factor
that sets into motion a sequence of gene activations

ultimately leading to formation of integrated testes from the

various embryonic cells in the urogenital ridge

15
Differentiation of Internal and External Genitalia

 Before the functioning of the fetal gonads, the primitive reproductive

tract includes a double genital duct system

—Wolffian ducts and Müllerian ducts

—and a common opening for the genital ducts and urinary system to
the outside.
 
 Normally, most of the reproductive tract develops from only one of
these duct systems:

 In the male, the Wolffian ducts persist and the Müllerian ducts regress,
whereas in the female, the opposite happens.
 

16
 The external genitalia in the two sexes and the vagina do not develop
from these duct systems

but from other structures at the body surface

 Which of the two duct systems and types of external genitalia develops
depends on the presence or absence of fetal testes.
 
 These testes secrete

(1) testosterone, from the Leydig cells, and

(2) a protein hormone called Müllerian-inhibiting substance (MIS) from

the Sertoli cells.
 
 MIS acts as a paracrine agent to cause the Müllerian duct system to
degenerate.
 
 Simultaneously, testosterone causes the Wolffian ducts to
differentiate into the epididymis, vas deferens, ejaculatory duct, and
17
seminal vesicle.
Externally and somewhat later, under the influence of testosterone
(after its conversion to DHT), a penis forms, and the tissue near it fuses
to form the scrotum.

The testes will ultimately descend into the scrotum, stimulated to do so

by both MIS and testosterone.

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19
In contrast, the female fetus, not having testes (because of the absence
of the SRY gene), does not secrete testosterone and MIS.

In the absence of MIS, the Müllerian system does not degenerate but
rather develops into uterine tubes and a uterus.

In the absence of testosterone, the Wolffian ducts degenerate, and a

vagina and female external genitalia develop from the structures at the
body surface

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21
 Ovaries, though present in the female fetus, do not play a role in these
developmental processes;

female development will occur automatically unless stopped from

doing so by the presence of secretions from functioning testes.
 
 There are various conditions in which normal sex differentiation does
not occur.
 
 For example, in the syndrome known as testicular feminization (or
androgen insensitivity syndrome),

the person’s genetic endowment is XY and testes are present, but he

has female external genitalia, a vagina, and no internal duct system at
all.
 
The problem causing this is a lack of androgen receptors due to a genetic
mutation.

22
Under the influence of SRY, the fetal testes differentiate as usual, and
they secrete both MIS and testosterone.

MIS causes the Müllerian ducts to regress, but the inability of the
Wolffian ducts to respond to testosterone

causes them to regress, and so no duct system develops.

 
The tissues that give rise to external genitalia (and the vagina, in the
female) are also unresponsive to testosterone,

so female external genitalia and a vagina develop rather than male

structures.

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24
Summary
 
1. The physiological basis of reproduction is procreation.
 
2. Components of Sexual Developments:
 
a. Recombination of the sex chromosomes (X & Y) at the time of
fertilization
b. Development of Gonads
c. Hormonal control of development of internal & external genitalia
d. Development of male or female phenotype
e. Differentiation of sexual behaviour
(Genetic sex  Gonadal sex  genital sex  Psychological
sex).

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3. Evidence that the Y chromosome is involved in testes formation:
 
a. XO women are female and without testes.

b. XXY humans are with Klinefelter Syndrome are males with testes.

c. Absence of portion of Y chromosome results in female phenotype.

26
4. Male phenotypic sexual differentiation is induced by 4 hormonal signals
in sequential order:
a. Müllerian duct inhibitory hormone
b. hCG (fetal placenta)
c. Testosterone
d. Dihydrotestosterone
 
5. Ovary has no role in sex differentiation of the female genital tract.

(In the absence of SRY-gene, hormone, gonads, the female sex

differentiates).

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29
The Male Reproductive System
 a series of ducts and tubules.
 TESTES
 EPIDIDYMS
 DUCTUS DIFFERENS
 URETHRA
 PENIS
 ACCESSORY GLANDS
 - PROSTATE

 - SEMINAL VESICLES
 - BULBOUERTHRAL GLANDS
.
 Cont…
1.Gametogenic: Production of male germ
cells, spermatozoa.
2.Endocrinologic: Production of male sex
hormones, androgens.
3.Reproductive:-
–Deposition of the spermatozoa in the female
genital tract.
–Maintenance of the species

32
 The Male sex organs
• The Gonads (Testes):
– Constitutes the primary sex organ
– Concerned with spermatogenesis
– And secretion of sex hormones (testosterone)

• The secondary (accessory) sex organs:

includes:

33
 Cont…
• The epididymis:
– system of coiled tubes in which sperm matures and
acquire motility.
– 6m long
• The vas deferens:
– Long duct that transports sperm from epididymis to the
urethra by contraction of its walls.
• The seminal vesicle:
– Coiled tubular gland, 2 in number (on each side of
prostate)
– secretes viscid yellowish fluid during intercourse. Which is
used for nutrition of sperm.

34
 Cont…
– Its duct end joins the end of vas deferens forming
the ejaculatory duct, which passes through the
prostate and opens into the prostatic urethra.

35
 Cont…
• The prostate:
– Large gland that surrounds the upper part of
urethra
– Secrete slightly alkaline fluid which is important
for successful fertilization of the ovum.

36
 Cont…
• The bulbourethral (cowper’s) gland:
– Secrete mucus during sexual excitement to
neutralize the acidity in the urethra before flow of
sperm.
• Penis:
– Erectile tissue
– Introduces the sperms into female genital tract
through sexual intercourse.

37
38
Structures and functions of the Testes
• Has 2 types of specialized tissues
1.Seminiferous tubules: form 90% of testicular
mass
a) Germinal cells: concerned with spermatogenesis
b) Sertoli cells: (non germinal)

2.Interstitial cells (Leydig cells)

39
 Functions of Sertoli cells
1. The spermatids mature in deep folds in the
cytoplasm of these cells
2. They secrete the following
a) Androgen binding protein (ABP): which maintains a
high and stable supply of androgen in tubular fluid.
b) Inhibin – inhibits FSH secretion from the anterior
pituitary gland.
c) Mullerian inhibiting substance (MIS): causes
regression of Mullerian ducts in males during fetal
life

40
 Spermatogenesis
• During formation of the embryo, the
primordial germ cells migrate into the testes
and become immature germ cells called
spermatogonia (within the outer region of the
seminiferous tubules)

• At puberty the spermatogonia begin to

undergo mitotic division and pass through
different stages to form mature sperms
41
 Steps in spermatogenesis

• Spermatogenesis occurs as the result of

stimulation by ant. pituitary gonadotropic
hormones and continue throughout
remainder of life but decreasing markedly in
old age.

42
 Cont…
• only about 1,000 to 2,000 stem cells migrate
into the embryonic testes. In order to produce
many millions of sperm throughout adult life
• In the first stage of spermatogenesis, the
spermatogonia migrate among Sertoli cells
toward the central lumen of the seminiferous
tubule these spermatogonia duplicate
themselves by mitotic division to form
primary spermatocyte.

43
 Cont…
• One of the primary spermatocytes undergo
meiotic division.

• In this way, spermatogenesis can occur

continuously without exhausting the number
of spermatogonia.

44
 Cont…
• When a diploid primary spermatocyte completes
the first meiotic division (at telophase I), the two
haploid cells thus produced are called secondary
spermatocytes.
• The two secondary spermatocytes undergo
second meiotic division to produces two haploid
spermatids.
• One primary spermatocyte therefore produces
four spermatids.
45
46
 The Spermatozoa
• Development of these interconnected
spermatids into separate mature spermatozoa
requires the participation of the Sertoli cells
this process is called spermiogenesis

• The entire period of spermatogenesis, from

spermatogonia to spermatozoa, takes about 74
days

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48
49
Events of Spermiogenesis (Spermatid  Spermatozoon)
a. Formation of acrosome.
b. Condensation and elongation of nucleus
c. Formation of mid-piece and flagellum
d. Discharge of organelles and cytoplasm not required

50
Spermatozoon
Anatomy:
a. Head
• Nucleus: n number of chromosomes
(23 chromosomes)
• Acrosome: enzymes needed to
penetrate the ovum.
b. Mid-piece
• Mitochondria: provides ATP for locomotion
c. Tail
• Flagellum: 9+2 array of microtubules (propels the spermatozoon)
51
Normal Vs Abnormal

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53
 The Spermatozoa
• It takes about 74 days to form a mature
sperm.
• The sperm is a single motile cell formed of
head and tail
• The head is composed of mainly nucleus
which contain chromosome.
• The anterior part is covered by a thick cap
called acrosome

54
 Cont…
• Sperm mov’t is produced by its tail, the energy
for these is supplied from ATP synthesized
from the mitochondria.
• Normal sperm moves at 3mm/min (1-4
mm/min), reaches the uterine tubes in 30-60
minutes after ejaculation
• Their ability for fertilization is increased if they
spend some time there, this is called sperm
capacitation.

55
 Cont…
• when they are first expelled in the semen,
they are unable to fertilize ovum.

• However, on coming in contact with the fluids

of the female genital tract, multiple changes
occur that activate the sperm for the final
processes of fertilization.

56
 Cont…
• These collective changes are called
capacitation of the spermatozoa.

• This normally requires from 1 to 10 hours.

57
 Maturation of Sperms
Maturation of Sperm in the Epididymis
• After formation in the Seminiferous tubules, the
sperm require several days to pass through the 6-
meter-long tubule of the epididymis.
• After the sperm have been in the epididymis for
18 to 24 hours, they develop the capability of
motility,
• But are not motile due to inhibitory proteins in
the epididymal fluid still prevent final motility
until after ejaculation.
58
 Cont…
• 120 million sperm are produced each day.
• A small quantity of these can be stored in the
epididymis, but most are stored in the vas
deferens.
• They can remain stored, maintaining their
fertility, for at least a month.
• During this time, they are kept in a deeply
suppressed inactive state by multiple inhibitory
substances in the secretions of the ducts.
59
Factors that control Spermatogenesis
• In addition to healthy testes, the following
factors affect spermatogenesis
1.Hormones
• FSH:
– Helps in dev’t of sertoli cells.
– Acts to facilitate the last stages of spermatid
maturation and promote the production of ABP
(androgen binding protein)

60
 Cont…
• LH:
– Stimulates testosterone secretion from the
interstitial cells of the Leydig
• Testosterone:
– It helps in the development of spermatids in to
mature spermatozoa.
• Other hormones:
– Growth hormone and thyroxin control metabolic
functions of testes.

61
 Cont…
2. Temperature:
• Spermatogensis needs a lower T0 of about
320c. So this is maintained by:
a) The scrotal skin is thin (has little fat) and is
reach in sweat glands.
b) Heat loss is favored by heat exchange in a
countercurrent system between the
spermatic arteries and veins.

62
 Cont…
c) The scrotal muscles relaxes in hot weather to
draw testis away from high abdominal
temperature, and it contracts during cold to
bring the testis near the body.

63
 Cont…
3. Diet:
• Proteins: important in division of the germ
cells.
• Vitamins:
– Vit. A deficiency: causes keratinization of tubular
epithelium resulting in their atrophy
– Vit. E def: causes irreversible Seminiferous tubule
degeneration and sterility in rats.

64
 Cont…
4. Extrinsic factors
• Prolonged exposure to various types of
radiation ( x-rays, atomic or nuclear
radiation)
• Prolonged hypoxia
• Toxins and certain infections (eg Mumps)
• Excessive administration of estrogen also
depresses spermatogenesis (inhibit FSH
secretion from ant. Pituitary gland)
65
 Endocrine functions of Testis

The testes secrete three hormones

1. Testestrone from leydig cells

2. Inhibin

3. Estrogen

66
 Cont…
Testosterone
• Principal hormone of testes
• Is a steroid hormone
• Secreted at a rate of 4-9 mg/day in adult male
from the
– Leydig cells and
– to lesser extent from the adrenal cortex

67
 Cont…

• Masculinizing hormones.

• In some tissues, testosterone is not active by

itself and is converted to the physiological
active hormone dihydrostestosterone (DHT)
by 5 α-reductase enzyme.

68
 Cont…
• Testosterone is responsible for formation of
internal male genitalia and increase in muscle
mass as well as the sex drive and libido

• DHT is responsible for formation of external

male genitalia and enlargement of penis and
prostate as well as growth of facial hair and
recession of hair line.

69
70
 Testicular Estrogen
• concentration of estrogens in the seminiferous
tubules is high and probably plays an important
role in spermiogenesis.
1. Formed in Sertoli cells by converting testosterone
to estradiol.
2. larger amounts of estrogens are formed from
testosterone and androstanediol in other tissues
of the body, especially the liver, probably
accounting for as much as 80 per cent of the total
male estrogen production.
71
 Effects of Testosterone

During fetal life

• Activates mullerian inhibition factor (MIF).

• Stimulates the dev’t of male genital system

namely the external genitalia, scrotum, as well
as prostate and seminal vesicle.

72
 In adult at puberty

1. On male genitalia
• Stimulates dev’t of penis, scrotum, and testis.

• Enlargement of seminal vesicle,

bulbourethral gland and prostate gland.

73
 Cont…
2. On sex characteristics
• Voice: larynx enlarges, vocal cords become
thick and voice becomes deeper.
• Hair growth:
– beard appears, scalp hair with characteristic
temporal recession, pubic hair takes triangular
shape with apex up.
– Hair also appears in axilla, chest and general body
hair increases

74
 Cont…
• Body conformation:
– Broad shoulders with narrow pelvis
– Muscle enlargement.
• Skin:
– Increased thickness with increased sebaceous
gland secretion
• Mental:
– More aggressive, increased libido

75
 Cont…
3. On general Metabolism: anabolic
a) It increases metabolic rate by 5-10%
b) Muscle development:
– Increases muscle mass, improves strength
c) Bone growth and calcium retention
– Increases the total quantity of bone.
d) RBCs:
– It promotes RBC synthesis, thus males have
higher RBC count.
76
 Control of Testicular function
1. GnRH:
• Secreted from hypothalamus
• Stimulates secretion of FSH and LH from ant.
Pituitary
• Secreted intermittently

77
 Cont…
2. GTHs (LH, FSH):
• LH: control testestrone secretion
– Negative feedback: excess testosterone produce
–ve feedback inhibition, mainly on GnRH and
probably also on ant pit. To inhibit LH secretion.
• FSH: control spermatogenesis
– Negative feedback: when spermatogenesis
proceeds rapidly sertoli cells secrete inhibin. It
suppress FSH secretion on the ant pit.
78
 Cont…
– Conversely when there is decreased rate of
spermatogenesis, sertoli cells stop secreting
inhibin.
• Psychogenic factors:
– Different emotions affect the hypothalamic GnRH
release.
• Effect of HCG on fetal testis
– HCG stimulates the secretion of testosterone from
the fetal testis causing development of the male
sex organs. It acts as LH.
79
80
 Abnormalities of testicular function
• Hypogonadism
– Castration in adults
– Cryptorchidism
• Hypergonadism
– Androgen secreting tumors
– Gynecomastia

81
 Semen
• Semen: is the fluid ejaculated at the time of
orgasm, milky, whitish yellow. With average PH
of 7.5
• Contains
– Sperm cells and,
– Seminal plasma
• Seminal plasma
– 60% is from seminal vesicle
– 30 % from prostate
– 5 % from bulbouretheral gland and epididymis each
82
 Cont…
• Secretions from seminal vesicle contain
fructose 1.5-6.5mg/ml, which is main nutrient
for sperms, as well as flavin, ascorbic acid, and
prostagladins.

• Prostatic secretions contain spermine, citric

acid, zinc, acid phosphatase, cholestrol, and
phospholipids as well as fibrinolysin.

83
 Cont…
• The prostatic fluid gives the semen a milky
appearance, and fluid from the seminal vesicles and
mucous glands gives the semen a mucoid
consistency.

• The slightly alkaline prostatic fluid helps to neutralize

the acidity of the other seminal fluids during
ejaculation, and thus enhances the motility and
fertility of the sperm.

84
 Cont…
• Average volume per ejaculation is 2.5-3.5 ml,
with 1X108/ml sperms per ejaculation.
• All males with counts under 50 million/ml are
subfertile and
• Under 20 millions/ml are sterile.
• Spermatozoa start active motility after
ejaculation and reach the fallopian tubes 30-
60 minutes after copulation.

85
 Cont…
• Alkaline PH of semen provides protection of
sperms from the acid env’t in the vagina.
• Sperm survive in the female genital tract up to
24-48 hrs
• Usually only one sperm enters the ovum.

86
FEMALE REPRODUCTIVE ORGAN
 Cont….
• Female reproductive functions can be divided
into two major phases:
(1)Preparation of the female body for
conception and pregnancy, and

(2) The period of pregnancy itself.

88
 Cont…
• The female reproductive system must perform
five main functions:
• Oogenesis and ovulation- production and
release of oocytes.

• Fertilization- allowing the sperm and oocyte

to meet and fuse.

89
 Cont…

• Pregnancy- providing a suitable environment

for the fetus to grow.
• Parturition- expelling the fetus with minimal
trauma to the mother baby.
• Lactation- providing the baby with nutrition.

90
Physiologic anatomy of the female sexual
organs
• The principal organs of the human female
reproductive tract, the most important of which
are the ovaries, fallopian tubes, uterus, vagina,
vulva and breasts.

• Reproduction begins with the development of

ova in the ovaries.
91
 Cont…
• The vagina: distensible tubular passage that leads to
the uterus from the external genitalia.
• The uterus: a muscular organ in which the fetus grows.

• The fallopian tube, uterine tube, or oviduct: ova

discharged from the ovary pass through this tubes to
the uterus.

92
93
94
Oogenesis (gametogenic functions)
• In humans, no new ova are formed after birth; unlike
spermatogenesis.

• During fetal dev’t the primitive germ cells are called

oogonia.

• Which grow into immature ova called primary

oocyte. ovaries contain over 7 million primary
oocytes.

95
 Cont…
• Each primary oocyte is surrounded by single layer
of epithelial cells (granulosa cells) forming
primordial follicle.

• However, many undergo atresia (involution) before

birth.

• So at the time of birth there are only 2 million, 50%

of which are atretic.
96
 Cont…
• The million that are normal undergo first meiotic
division at about this time and enter a stage of arrest in
prophase in which those that survive persist until
adulthood.

• However follicular atresia continues, so number of ova

in both ovaries at puberty is about 300,000.

• Just before ovulation, the first meiotic division is

completed forming secondary oocyte.
97
 Cont…
• One of the daughter cells, the secondary oocyte,
receives most of the cytoplasm, while the other,
the first polar body, fragments and disappears.

• The secondary oocyte immediately begins the

second meiotic division, but this division stops at
metaphase and is completed only when a sperm
penetrates the oocyte.

• At that time, the second polar body is cast off

and the fertilized ovum proceeds to form a new
individual.
98
99
 Cont…
• The ovaries mature at puberty (average age 12years)
and stop activity at menopause (average age 50yrs.)

• Only one of these ova per cycle (or about 500 in the
course of a normal reproductive life) normally
reaches maturity; the remainder degenerate.

100
 The Sex cycle in Females
• Regular cyclic changes in the female reproductive
system
• Periodic preparation for fertilization and pregnancy.
• These cycles occur in the ovary (ovarian cycle), uterus
(menstrual cycle), vagina (vaginal cycle), uterine cervix
(cervical cycle)
• Start at puberty and stop at menopause.
• All occur secondary to ovarian cycle.
101
 Cont…

• At age 9 to 12 years, the pituitary begins to secrete

progressively more FSH and LH, which leads to onset
of normal monthly sexual cycles beginning between
the ages of 11 and 15 years.
• The most apparent is menstrual cycle b/c it is
characterized by vaginal bleeding (menstruation).

102
 Cont…
• Average duration of single cycle is 28 days from the
start of one menstrual period to the next.

• The first menstrual period that denotes puberty is

called menarche.

• However, the first event at puberty is thelarche (i.e.

dev’t of breasts) followed by pubarche (i.e. dev’t of
axillary and pubic hair)

103
 The Ovarian Cycle
• Consists of two phases
1. The follicular phase
• The ovaries are in the follicular phase from day one
of menstruation to ovulation (i.e. day 1-13 of cycle)

• Toward the end of the follicular phase only one

follicle reaches maturity and becomes graaphian
follicle.

106
 Cont…
• As follicle grows the granulosa cells secrete an
increasing amount of estradiol (the principal
estrogen) which reaches its highest
concentration in the blood at day 12, 2 days
before ovulation.

• The growth of follicles and secretion of

estradiol are stimulated by FSH secreted from
the anterior pituitary gland.

107
 Cont…
• FSH stimulate the production of FSH receptors
in the granulosa cells, these is further
augmented by estrogen which stimulates
production of new FSH receptors.

• The large amounts of estrogen from the most

rapidly growing follicle act on the
hypothalamus to depress further enhancement
of FSH secretion by the anterior pituitary gland,
in this way blocking further growth of the less
well developed follicles. 108
 Cont…

• Toward the end of the follicular phase FSH and

estrogen stimulate the production of LH receptors in
the graaphian follicle.
• The rapid rise of estrogen near mid cycle acts on the
hypothalamus to increase the frequency of GnRH
pulses.

109
 Cont…
• In addition it increases the ability of the pituitary
to respond to GnRH with an increase in LH
secretion (6-10x) and FSH (2-3X), through positive
feedback mechanism.

• As a result there is a burst of LH secretion called

LH surge.
• LH surge begins 24 hrs. before ovulation and
peaks about 16 hrs. before ovulation.
• It is this surge that causes full maturation of the
follicle and then triggers ovulation.
110
 Ovulation
• Rupture of the graaphian follicle and the release of
secondary oocyte arrested at metaphase II
surrounded by zona pellucida and corona radiata.

• The ovum is picked up by the fimbriated end of the

fallopian tube and is transported to the uterus where
it is fertilized or lost.

111
112
 2. The Luteal phase
• The follicle that ruptures at the time of ovulation promptly fills
with blood, forming what is sometimes called a corpus
hemorrhagicum.

• Minor bleeding from the follicle into the abdominal cavity may
cause peritoneal irritation and fleeting lower abdominal pain
("mittelschmerz").

• The empty follicle is stimulated by LH to become a new structure

yellowish, lipid-rich cells called luteal cells which develop to
corpus luteum, It secretes both progesterone and estrogen.
• .
113
 Cont…
• Progesterone levels rapidly rise to peak one week
after ovulation.
• These hormones prepare the uterine
endometrium for fertilization.
• If pregnancy occurs the corpus luteum persists
• However if there is no pregnancy the increased
levels of hormones inhibits (negative feedback)
the release of LH and FSH, so the corpus luteum
starts to degenerate (regress) on about day 24 of
the cycle(=luteolysis)
114
 Cont…
• it eventually involutes within 2 weeks.
• And is replaced by scar tissue called corpus albicans
• As a result of this the estrogen and progesterone
levels in the blood fall and this leads to release of
both FSH and LH from anterior pituitary which starts
a new cycle by stimulating dev’t of a new graafian
follicle.
115
116
 Uterine or endometrial cycle
• Cyclic changes that occur in the endometrium.
• The endometrium consists of two main layers

1. The superficial (functional layer):

– constitutes 2/3 of the endometrial thickness.
– Shed out with menstrual flow
– Supplied by coiled/spiral arteries.

117
 Cont…
2. Deep (basal) layer:
– this constitutes about 1/3 of the endometrial
thickness.
– Regenerates the functional layer after its shedding
– Supplied by straight basal arteries

118
 Cont…
• At the end of menstruation, all but the deep
layers of the endometrium have sloughed.

• A new endometrium then regrows under the

influence of estrogens from the developing
follicle.

• The endometrium increases rapidly in thickness

from the fifth to the fourteenth days of the
menstrual cycle.

119
120
 1. The Proliferative
phase( follicular or
•
preovulatory phase)
Starts after menstruation and continues till ovulation
• Coincides with the follicular phase of the ovarian
cycle.
• Under effect of estrogen from graafian follicle, the
endometrium increases rapidly in thickness (2-3mm
thick) due to rapid proliferation of its stroma.
• Uterine glands increase in length , but they do not
become convoluted or secrete to any degree.

121
 2. The Secretory phase (post
ovulatory or luteal phase)
• Starts after ovulation and continues till menstruation

• Coincides with luteal phase of ovarian cycle

• Under the influence of corpus luteum hormones

particularly progesterone
• Further thickening of endometrium (4-6mm) to
become ready for implantation of fertilized ovum

122
 Cont…
2. Increased blood flow in the endometrium
3. The glands become coiled and tortuous , and they
begin to secrete a clear fluid. Which is nutrient for
fertilized ovum before it implants so the
endometrium becomes slightly edematous

• So secretory phase prepares uterus for implantation

of fertilized ovum.

123
 3. The menstrual (destructive or
bleeding phase)
• This phase occurs if fertilization does not occur
• Averages 3-5 days.
• When the corpus luteum regresses, hormonal
support for the endometrium is withdrawn.
• The endometrium becomes thinner, which adds to
the coiling of the spiral arteries.
• Foci of necrosis appear in the endometrium, and
these coalesce.

124
126
 Cont…
• Blood loss during menses is about 30ml and
mostly arterial
• The blood does not clot because the
endometrial tissue contains fibrinolysin.

127
 Cont…
• The proliferative phase of the menstrual
cycle represents restoration of the epithelium
from the preceding menstruation, and

• The secretory phase represents preparation

of the uterus for implantation of the fertilized
ovum.

128
 Cont…
• The length of the secretory phase is
remarkably constant at about 14 days, and the
variations seen in the length of the menstrual
cycle are due for the most part to variations in
the length of the proliferative phase.

• When fertilization fails to occur during the

secretory phase, the endometrium is shed and
a new cycle starts.

129
 Menopause
• Cessation of the sex cycle and menstruation in
females.
• Menses becomes irregular and cease between the
ages of 45-55 yrs.
• This occurs due to:
1. Decline in number of primordial follicles
2. Unresponsiveness of the ovaries to GTHs
– Though there is increased secretion from ant.
Pituitary by absence of –ve feedback mechanism

130
 Cont…
• The decrease in ovarian hormone specially
estrogen leads to
1. Osteoporosis and wasting: due to loss of anabolic
effect of estrogen
2. Regression of the secondary sex characteristics
3. Atrophy of the accessory sex organs
– Uterine endometrium and vaginal epithelium
4. Psychic sensations
– Dyspnea, irritability, anxiety, fatigue, headache,
dizziness

131
 Cont…
5. Vasomotor disturbances
– Commonly hot flushes: a sensation of warmth
spreading from the trunk to the face, associated with
skin flushing and sweating.
– Hot flushes are said to occur in 75% of menopausal
women and may continue intermittently for as long as
40 years.
– Their cause is unknown. However, they coincide with
surges of LH secretion.

• So daily administration of small dose of estrogen

reverses the symptoms.
132
The Ovarian Hormones

133
 Estrogens
• Steroid hormones
• Secreted by:
1. The ovaries (the granulosa cells of the ovarian
follicles, luteal cells of corpus luteum)
2. The placenta
3. The adrenal cortex (in small amounts)

134
Types and biosynthesis of estrogen
• Three types of estrogens
1.Estradiol (most potent)
2.Estrone (less potent)
3.Estriol (least potent)

• Estradiol is formed by aromatization of

testosterone

135
 Actions of Estrogens
1. On primary sex organs (gonads)
– Growth of follicles, formation of corpus
luteum by stimulating LH surge.

136
 Cont…
2. On secondary (accessory sex organs):

• The uterus: growth of endometrial epithelium and

glands, increase in uterine blood flow as well as increased
response to oxytocin.

• The fallopian tube: increase their motility

• The uterine cervix: makes cervical mucus thin and

alkaline
137
 Cont…
• The vagina: cause cornification of vaginal
epithelium and increase acidity of vaginal
secretion (protect from infection)
3.On female secondary sex characteristics:
• They are feminizing hormones (produce body
changes in girls at puberty
• Body changes: narrow shoulders, broad hips,
convergence of thighs, divergence of arms
( wide carrying angles)
138
 Cont…
• Fat distribution: deposited in the breasts, buttocks,
and lower abdomen.
• The larynx is not enlarged by estrogens, so voice
remains high pitched
• Body hair: less body hair and more scalp hair and
characteristic pattern of pubic hair (triangular with its
base up)
– The growth of pubic and axillary hair is caused
mainly by androgens (from the adrenal cortex and
ovaries)
139
 Cont…
4. Psychological and behavioral changes: increased
libido.
5. On mammary glands: promote duct growth, breast
enlargement and pigmentation of areolas.
6. On endocrine organs:
• Control GTHs by –ve and +ve feedback mechanism
7. On metabolism:
• Exert protein anabolic effect
• Cholesterol lowering action
140
 Cont…
• Skin: cause the skin to develop a texture that is soft
and usually smooth.

141
 Progesterone

• A steroid hormone.

• Secreted by

1.Corpus luteum

2.The placenta

142
 Actions of progesterone
• Helps maintenance of pregnancy (so it is called
the hormone of pregnancy) through
1. On the uterus:
• Characteristics changes in the endometrium
during the secretory phase, which is essential for
embedding and implantation of the fertilized
ovum and formation of placenta
• It decreases uterine response to oxytocin, thus
promoting relaxation of the uterus (which is
essential for maintenance of pregnancy)
143
 Cont…
2. On the uterine cervix and vagina: characteristic
changes during luteal phase.

3. On ant pituitary and hypothalamus:

• Inhibits LH secretion by –ve feedback mechanism, so
it can prevent ovulation and produce contraception.
• Together with high estrogen levels it inhibits the
release of GTHs during pregnancy

144
 Cont…
4. Body temperature: is thermogenic and is
probably responsible for the rise in basal body
temperature at the time of ovulation.

5. In high doses produces natriuresis (probably by

blocking the action of aldosterone on the
kidneys)
6. Breasts: stimulates the development of lobules
and alveoli. Supports the secretory function of
the breast during lactation.
145
Abnormalities of ovarian functions
• Occur as a result of either ovarian disorders or a
variety of diseases (specially hypothalamic or
pituitary)
1. Anovulatory cycle
2. Menstrual abnormalities
• Amenorrhea: absence of menses
– Primary: if menstruation never occurred
– Secondary: if it occurs in women with previous
normal periods.

147
 Cont…
• Oligomenorrhea: little menstrual flow
• Menorrhagia: profuse menstrual flow
• Metrorrhagia: irregular uterine bleeding.
• Polymenorrhea

148
Pregnancy

149
 Fertilization
• Takes place in the mid portion of the uterine tube
• Millions of sperms are deposited in the vagina
but only 50-100 reach the ovum
• Acrosomal reaction: facilitates the penetration of
the sperm through the zona pellucida, by
secretion of acrosin
• Fusion of one sperm with the ovum cause
structural change in the ZP which prevent
polyspermis
• This results in zygote formation

150
 Cont…
• Zygote divides mitotically producing blastocyst.
• Reaches uterus within 3 days and stays another 3
days in uterine cavity before implantation.
Implantation:
• Occurs at about the 7th day after fertilization
• It implants on posterior fundus.
• Is followed by dev’t of placenta.

151
152
155
 Placenta
• Developmental and Physiologic Anatomy of
the Placenta
• While the trophoblastic cords from the
blastocyst are attaching to the uterus, blood
capillaries grow into the cords from the
vascular system of the newly forming embryo.
.

156
157
 Placenta
• Developmental and Physiologic Anatomy of
the Placenta
• While the trophoblastic cords from the
blastocyst are attaching to the uterus, blood
capillaries grow into the cords from the
vascular system of the newly forming embryo.
.

158
159
 Cont…
• Note that the fetus’s blood flows through two
umbilical arteries, then into the capillaries of the
villi, and finally back through a single umbilical vein
into the fetus.
• At the same time, the mother’s blood flows from her
uterine arteries into large maternal sinuses that
surround the villi and then back into the uterine
veins of the mother.

160
 Cont…

• The total surface area of all the villi of the mature

placenta is only a few square.
• Nutrients and other substances pass through this
placental membrane mainly by diffusion.

161
 Cont…
• Diffusion of Oxygen Through the Placental
Membrane.
• The dissolved oxygen passes into the fetal blood
by simple diffusion, driven by an oxygen
pressure.

• the mean PO2 of the mother’s blood in the

placental sinuses is about 50 mm Hg, and the
mean PO2 in the fetal blood after it becomes
oxygenated in the placenta is about 30 mm Hg.
162
 Cont…
• Diffusion of Carbon Dioxide Through the
Placental Membrane.
• The only means for excreting the carbon
dioxide from the fetus is through the placenta
into the mother’s blood.

• The PCO2 of the fetal blood is 2 to 3 mm Hg

higher than that of the maternal blood.

163
 Cont…
• Diffusion of Foodstuffs Through the Placental
Membrane.
• Other metabolic substrates needed by the
fetus diffuse into the fetal blood in the same
manner as oxygen does.
• Glucose diffusion is aided with facilitated
diffusion process.
• Fatty acids cross the membrane through
simple diffusion
164
 Cont…
• Excretion of Waste Products Through the Placental
Membrane.
• In the same manner that carbon dioxide and other
excretory products diffuses from the fetal blood into
the maternal blood, and are then excreted along
with the excretory products of the mother.
• These include especially the nonprotein nitrogens
such as urea, uric acid, and creatinine.

166
 Placental hormones
• important in the maintenance of pregnancy and for
the preparation of the body for parturition and
lactation.

167
 Cont…
The major peptide hormones secreted by the placenta
are:
1) Human chorionic gonadotrophin (hCG)
2) human placental lactogen

•The major placental steroids are:

3) Estrogen
4) Progesterone

168
 Cont…
• Human Chorionic Gonadotropin (hCG) and its
effect to cause persistence of the corpus
luteum and to prevent menstruation.

• So that progesterone secretion continues,

shading of uterine endometrium is prevented
and spontaneous shading of the endometrium
is inhibited.

169
 Cont…
• Luteal progesterone is needed for the first 6-8
weeks of pregnancy.

• After this time the placenta takes over as the

main source of progesterone.

• Under the influence of human chorionic

gonadotropin, the corpus luteum in the mother’s
ovary grows to about twice its initial size by a
month.

170
 Cont…
• hCG may exert a direct effect on maternal
hypothalamus to inhibit the synthesis of FSH. If so,
this might contribute to the suppression of ovulation
during pregnancy.

• hCG possesses immunosuppressive activity which

may prevent the mother rejecting the fetus as
foreign tissue.

171
 Cont…
• hCG exerts a stimulatory effect on the leydig cells of
the testis in the male fetuses and plays a part in the
differentiation of the male reproductive tract.

• hCG becomes detectable in the plasma at around

seven days after the time of conception and in urine
two weeks after.

172
 Cont…
2) Human placental lactogen (hPL) :
•hPL contributes to proliferative changes seen in the
mammary tissue in preparation for lactation and exerts
important metabolic effects in the mother.

•It stimulates an increase in the maternal plasma levels

of glucose, aminoacids and free fatty acids.

173
 Cont…
3. Secretion of steroids by the Placenta
• The placenta, like the corpus luteum, secretes
both estrogens and progesterone starting
around 10 weeks

• Steroid hormones (estrogen and

progesterone) are produced in large amounts
by the placenta through out gestation.

174
 Parturition
• It means birth of the baby.
• The duration of pregnancy in humans averages 270
days from fertilization (284 days from the first day of
the menstrual period preceding conception).

• Toward the end of pregnancy, the uterus becomes

progressively more excitable, until finally it develops
such strong rhythmical contractions that the baby is
expelled.

176
 Hormonal Factors
• Increased ratio of estrogens to progesterone.
• Progesterone inhibits uterine contractility during
pregnancy, thereby helping to prevent expulsion of
the fetus

• Conversely, estrogens have a definite tendency to

increase the degree of uterine contractility,

177
 Cont…
• From the seventh month onward, estrogen
secretion continues to increase while
progesterone secretion remains constant or
perhaps even decreases slightly.

• Therefore, it has been postulated that the

estrogen-to-progesterone ratio increases
sufficiently toward the end of pregnancy to be at
least partly responsible for the increased
contractility of the uterus.
178
 Cont…
Effect of Oxytocin on the Uterus.
•Oxytocin causes uterine contraction .
•There will be increased oxytocin receptors at
uterine smooth muscles .
•Stretch of the uterus and cervix increases
uterine contractility
•In addition stretch of cervix elicit reflex which
result in production of oxytocin from the post.
Pituitary.
179
180
 Lactation
• Development of the Breasts
• In general, estrogens are primarily responsible for
proliferation of the mammary ducts and
progesterone for the development of the lobules.

• During pregnancy, prolactin levels increase

steadily until term, and levels of estrogens and
progesterone are elevated as well, producing full
lobulo alveolar development.
181
 Cont…
Secretion & Ejection of Milk
• Prolactin cause the formation of milk droplets and their
secretion into the ducts.

• Oxytocin causes contraction of the myoepithelial cells

lining the duct walls, with consequent ejection of the milk
through the nipple.

•The reflex release of oxytocin is initiated by touching the

nipples and areolas (milk ejection reflex).

182
 Initiation of Lactation after Delivery

• The breasts enlarge during pregnancy in

response to high circulating levels of
estrogens, progesterone, prolactin, and
possibly hCG.
•

183
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