Physiology

of Human
Reproductive & Development
1

System

DR. RADIAH ABDUL GHANI

DEPARTMENT OF BIOMEDICAL SCIENCE
 Background
2

Reproductive is one area in physiology in which

human system is complicated.

Human sexually dimorphic, reflects by sex hormones.

Current debate: whether we are behaviorally and

psychologically dimorphic as well?

Current study in mammals: It appears that at least

part of our behavior is established before we ever leave
the womb.
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Where do we start?
Age-old question

4
 Learning Objectives
5

Describe the process of sex determination in human.

Male reproductive system: testes and sperm production,
hormonal control of spermatogenesis, male accessory gland
and other effects of estrogen.
Female reproductive system : ovary, menstrual cycle, effects
of androgens.
Hormonal regulation of reproductive system.
Describe the pregnancy and parturition
Explain growth and aging related with reproductive system.
Relate with Islamic perspective.
 Introduction
6

System consists of:

- Gonads (seed) are the organs produce
gametes (to marry)
- Internal accessory ducts and glands.
- External structures known as genitalia.
 In human..
7
46 chromosomes : 22 matched pairs of autosomes
+
1 pair of sex chromosomes

 XX (default) or XY
 Y : essential for dev of male reproductive organ.
 X : unique genes for development
Genetic sex is determined by sex
chromosomes
8
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XO- infertile, need XX for functional ovaries

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 Secret of Sexual development
11

- Reproductive structures start to develop until the 7th

week of development (embryo stage), or second
months of development.
- Before that, the structure is at bipotential stage.
- Bipotential : genital turbicle, urethral fold, urethral
groove and labioscrotal swelling.
- These structures differentiate later.
- The role of region Y on Y chromosomes – containing
SRY gene. (The secret is locked within the
human genome)
SRY Gene
12
 Role of SRY gene
13
Sex-determining region of Y
chromosome in embryonic germ
cells (SRY gene)

produces

Testis Determining
Factor (TFD)

Initiates
production of

Multiple proteins that cause

gonad to differentiate into a testis

Which has
 Leydig cells 14 Sertoli cells

secrete
Mullerian
Testosterone Inhibiting
Substance

controls
causes

- Development of Wolfian
Duct into accessory
structures. - Regression of Mullerian duct
- Development of male
external genitalia.
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Sexual Differentiation
16

Castrate: Remove the testicles

17
 Why was Sultan Abu
Shah VIII of
Palembang wrong to
blame his wives when
they are unable to
produce a male heir to
the throne?

18
 Pseudo (false) + hermaphrodites
19

 These men have the internal sex organs but

inherit a gene that cause deficiency in one of
the male hormones.
 Due to enzyme deficiency, male external
genetalia and prostate gland fail to develop
fully during fetus stage.
 At birth, the infants considered as female.
 However, at puberty, the testes again begin to
secrete testosterone, causing masculinization.
20
How about pseudo hermaphrodites
in female?

21
 The actual
article is
uploaded in i-
ta’aleem.

22
 True hermaphrodites
23

 An individual has both ovarian and testicular tissue.

The ovarian and testicular tissue may be separate, or
the two may be combined in what is called an
ovotestis.
 The external genitals may be ambiguous or may
appear to be female or male.
 In most people with true gonadal intersex, the
underlying cause is unknown, although in some
animal studies it has been linked to exposure to
common agricultural pesticide.
Hermaphrodites: A View from Science and
Faith

24
The role of endocrine system
25
Endocrine and Reproductive systems
26

- A hypothalamic releasing hormone GnRH, controls

the secretion from anterior pitutary : FSH & LH
which in turns act on gonads.
- FSH + steroid sex hormone regulate the
gametogenesis.
- LH acts primarily on endocrine cells, stimulating of
steroid sex hormones such as androgens, estrogens
and progesterone.
- Estrogen dominate in female and androgens in male.
- Also from gonad itself, secrete peptide hormones
that act on pituitary such as inhibins (-FSH)
- Feedback pathway is important.
Male Reproductive System
27

 Spermatogenesis
 Semen secretions
 Male endocrine system
 Important Cells in Male
28

 Sertoli cells -→ the function is to regulate the

development of spermatogonia into sperm. They also
provide sustenance for the developing sperms. It also
secrete a variety of proteins.
 Leydig cells → The function is to produce
testosterone. It is active in fetus, to develop from
bipotential stage into male characteristic. After birth
it is inactive until puberty. At that time, they resume
their production of testosterone. 95% of testosterone
produced by leydig cells, 5% from adrenal cortex.
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Why the composition of semen
is highly important for sperm?
32
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HORMONE CONTROL IN MALE

34
 Hormonal Regulation of sperm and testosterone
in men.
• Hypothalamus secretes gonadotropin-releasing hormone
(GnRH).
– Stimulates anterior pituitary to secrete:
• Follicle-stimulating hormone (FSH).
– Binds to Sertoli (sustenance cells)
– Promotes sperm production.
• Luteinizing hormone (LH).
– Leydig Cells
– Controls testosterone production.
» Testosterone is essential for reproductive
organs and male secondary sex characteristics.
•
35
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
 In pseudohermaphrodites
36

 These men inherit a defective gene for the enzyme 5-

alpha-reductase which catalyzes the conversion of
testosterone to dihydrotestosterone (DHT).
 Because of deficient of DHT, the male external
genetalia and prostate gland fail to develop during
fetal development, despite normal testosterone
secretion by testes.
 What happened at birth? Male or female?
 What happened at puberty?
 37

FEMALE REPRODUCTIVE SYSTEM

OVARY : PRODUCE OVUM AND HORMONES

38
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FEMALE REPRODUCTIVE PHYSIOLOGY
40

MENSTRUAL CYCLE
OOGENESIS
FERTILIZATION
PREGNANCY
DELIVERY
MENOPAUSE
Menstrual Cycle: Ovarian cycle; Uterine cycle

• Follicular phase
• Egg matures
• Ovulation
• Egg released
• Luteal phase
• Corpus luteum
• Endometrium
• Prep for blastocyst
• No Pregnancy
• Menses
41 Figure 26-13: The menstrual cycle
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
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THE MENSTRUAL CYCLE

43
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Ovulation

• 16-24 hours after LH

surge; the mature follicle
secretes collagenase
• Egg breaks out of the
follicle
• The egg “awaits”
fertilization in the
fallopian tube.
• The follicle “leftovers”,
differentiate into the
corpus luteum.

45
Early to Mid-Luteal Phase
• Corpus Luteum produces
• Progesterone (dominates)
• Estrogen somewhat increases
• Endometrium prepares for a fertilized egg
(blastocyst)
• Another effect of PG:
» Lipid and glycogen stores
» Thickening of cervical mucus (prevent
bacterial growth)
» increase in temperature (thermogenic
ability) 46
Late-Luteal Phase and Menstruation

• Corpus luteum: 12 day life span

– Apoptosis; programmed death
• Estrogen/progesterone levels fall
• Thickened endometrium cannot be
maintained
• Menses occurs about 2 days after corpus
luteum degeneration.

47
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
48
Estrogens and Androgens control secondary
Sex characteristics in women
49

 Estrogen : control the development of primary and

secondary sex characteristics in females, just as
androgens control them in males.
 In women, the most prominent secondary traits are
the female pattern of fat distribution and breast
development.
 Pubic and axillary (armpit)n hair growth is under the
control of adrenal androgens, as in libido or sex
drive.
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PREGNANCY AND
PARTURITION
 Capacitation
51

 Once egg is released from ruptured follicle, it is

swept into the Fallopian tube on currents created by
the beating cilia.
 Meanwhile, sperm deposited in the vagina must go
through their final maturation step, called
capacitation.
 Capacitation of sperm confers the ability to swim
rapidly and fertilize eggs.
 The process is not well understood, but it involves
the removal of glycoprotein from the sperm’s head.
 This process took place in female reproductive tract.
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 Capacitation in IVF?
53
 The sperm must be artificially capacitated by
physiological salines supplemented with human
serum before being exposed to the harvested eggs.
 Fertilization
54

 Fertilization of an egg by a sperm is the result of a

chance encounter, aided by chemical attractants
produced by egg.
 An egg can be fertilized for about 12-24 h after
ovulation- sperm remain viable for about 3-4 days.
 To reach protected egg, a sperm must penetrate
several layers:
- Outer layer of loosely granulosa cells.
- Protective glycoprotein coat of zona pellucida.
 55

 To get pass these barriers, capacitated sperm release

powerful enzymes from the acrosome in the sperm
head, a process known as acrosomal reaction.
 This enzyme dissolve cell junctions and the
glycoprotein coat, allowing sperm to wiggle their way
to the egg.
 The first sperm to reach the egg quickly finds sperm-
binding receptors on the membrane and fuses its
membrane to the oocyte membrane.
 The fused section of membrane opens, and the
sperm nucleus sinks into the cytoplasma of the egg.
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 Fusion of sperm and egg to form a zygote
57

2nd meiotic division occurs upon fertilization

Figure 26-17: Fusion of sperm and egg to form a zygote

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

 Cortical Reaction
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 Another process initiated by egg sperm fusion.

 This chemical reaction is designed to prevent
polyspermy.
 Membrane bound cortical granules release their
content into a space just outside the oocyte
membrane.
 This alter the membrane so that additional sperm
cannot penetrate or bind.
Zygote Development: Cell Division & Implantation
59

Ovulation, fertilization, and implantation of an ovum

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

 The dividing zygote takes about 4 days to move from
distal end of fallopion tube into uterine cavity.
 Under influence of progesterone, the smooth muscle
of the tube relax and transport it slowly.
 By the time it reach to uterine, the developing
embryo consists of a hollow ball of about 100 cells.
 This is called a blastocyst.
 Outer layer of blastocysts become chorion, and later
a placenta.
 Inner layer will develop into the embryo.
 Other extraembyonic membranes – form allantois,
then umbilical part.

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Outer blastocyst cells become the CHORION and forms the
placenta; inner portion becomes the embryo

61
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
 The Placenta

– As the embryo implants in uterine and the

placenta begin to form, the corpus luteum is
coming to the end of its life (12-day).
– Unless the embryo sends a hormonal signal,
corpus luteum disintegrate, progesterone and
estrogen levels drop, and the embryo will be
washed from the body along with menses.
– The hormone that prevent this, coming from
placenta

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–Fingerlike chorionic
villi penetrate the
endometrium
–Placental enzymes
breakdown maternal
blood vessels
–Embryo and maternal
blood do NOT mix! The
placenta is a barrier; but
nutrients do cross
– secrete progesterone.

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 Hormones secreted by placenta
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 Human chorionic gonadotrophin

- The signal that keeps the corpus luteum active
during pregnancy.
- Under influence of hCG, the corpus luteum keeps
producing progesterone to keep endometrium intact.
- However, by 7th week of development, the placenta
will fully take over progesterone production.
- Corpus luteum is no longer needed, it will finally
degenerates.
- hCG peaks at 3 months, then diminishes.
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 Second function of hCG, stimulate the testosterone

production by developing testes in male fetuse.
 Fetal testosterone and its metabolite, DHT are
essential for expression male characteristics and for
descend of the testes into the scrotum before birth.
Human Chorionic somatomammotropin
68

 hCS also known as hPL (human placental lactogen).

 Structurally related to growth hormone and
prolactin.
 Contribute to breast development and milk
production.
 Also regulates mothers’ metabolism- extra glucose.
 However, many unanswered questions about its
function.
 Estrogens and progesterone
69

 Both are produced continuously during pregnancy.

 First by corpus luteum, later by placenta.
 Estrogen : contributes to the development of the
milk-secreting ducts of the breast.
 Progesterone: essential for maintaining the uterus
wall in addition helps surpress uterine contraction,
along with relaxin.
 Placenta making up other hormones including
inhibin, prolactin.
 PARTURITION (birth process)
70

Pregnancy ends with labour and delivery ☺

- Parturition normally occurs in the 38th – 40th week
of gestation.
- Begins with labour – rhythamic contraction of
uterus designed to push the fetus out into the
world.
- Signals : from mother, or fetus, or both.
- Mother : drop of progesterone levels (Pg inhibits
uterine contraction).
- Fetus : signal that he has a complete development.
- However, exact cause/signal is still unknown.
 A signal for birth
 As the pregnancy nears full term, the number of
uterine oxytocin receptor increases.
 Synthetic oxytocin – induce labour. 50-50.
 Prostaglandins, produced in response to oxytocin
secretion.
 Very effective at causing uterine muscle contractions.
 As the contraction intesify, the fetus moves down
through birth canal.
 The placenta detaches from uterine wall, and is
expelled short time later.
 The contraction of the uterus clamp the maternal
blood vessels and help to prevent excessive bleeding.
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 The mammary gland secrete Milk
74

When infant is born, it loses its source of maternal

nourishment through placenta and rely on external
source.
Human milk is the best food for babies especially
from birth day up to 6 months.
 During pregnancy, the mammary glands develop
under estrogen influence, aided by growth hormone
and progesterone.
 However, hormone that really induce milk
production is prolactin from anterior pituitary.
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 Prolactin
76

 During later pregnancy stage, prolactin level in blood

increases (10 times compared to non-pregnant).
 Despite high level, the mammary gland produce only
small amounts of a thin, low-fat secretion called
colustrum because the level of estrogen and
progesterone high.
 After delivery, when estrogen and progesterone
decreases, the gland begins to produce greater
amounts of milk.
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 Breastfeeding
78

 Suckling, a mechanical stimulus of infant’s nursing

at breast, increase the prolactin secretion, resulting
milk production.
 Pregnancy is not required for lactation – adopted
baby case.
 The ejection of milk – let-down reflex, requires the
presence of second hormone known as oxytocin.
 Oxytocin initiates smooth muscle contraction in
breast and uterus.
 Uterine contraction help return the uterus to a pre-
pregnancy size.
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OTHER ISSUES
 Infertility

- Problem may arise from either male or female or

both.
- Male: low sperm count, high number of defective
sperms.
- Female: hormonal problem, blockage of fallopion,
cyst..
- Both:production of AB to sperm by female
- In vitro fertilization – female hormones is
manipulated to ovulate many eggs at one time.The
eggs are collected and surgically fertilised outside the
body. The developing embryos are then placed in the
women’s uterus which has been primed for
pregnancy by hormonal therapy.
Fertile men: Infertile men:

• A sperm count over 48 • sperm counts below 13.5

million per milliliter of million,
semen, •
• more than 63% of the • less than 32% sperm
sperm were moving motility
(sperm motility), and
•
• more than 12% of the
sperm had a normal shape • fewer than 9% of the
and structure (sperm sperm had a normal
morphology). appearance.
•

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Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
 Undescended Testes
86

- 3% of male children are born with undescended testes where they

remain in the abdominal cavity instead of moving down into the
scrotum.
- 80% of undescended testes will descend on their own by 1 yr, or
else they must be helped along medically.
- Undescended testes are called cryptochodism and can be unilateral
or bilateral.
There are 2 reasons for concern:
Fertility—if the testes are at the wrong temperature, sperm will not
be produced and the man will be infertile.
There’s a high incidence of testicular cancer in men with
undescended testes.
If only 1 is undescended fertility will not be a problem, but there is
still an increased risk for cancer.
 Misscarriage & Stillbirth
88

- the natural death of an unborn human while it is

still an embryo or fetus in its mother's womb.
- a death takes place in the early stages of prenatal
development prior to fetal viability (the stage of
potential independent survival).
- The danger of a miscarriage is the most common
complication of early pregnancy in human.
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 Causes: first trimester
90

 - Most clinically apparent miscarriages (two-

thirds to three-quarters in various studies)
occur during the first trimester
 - Chromosomal abnormalities are found in
more than half of embryos miscarried in the
first 13 weeks.
 Progesterone deficiency may be another
cause.
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 Causes: second trimester
 -Up to 15% of pregnancy losses in the second
trimester may be due to uterine
malformation, growths in the uterus
(fibroids), or cervical problem.
 These conditions also may contribute to
premature birth.
 One study found that 19% of second trimester
losses were caused by problems with the
umbilical cord.
 Problems with the placenta also may account
for a significant number of later-term
miscarriages.
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 Stillbirth
A stillbirth occurs when a fetus has died in the uterus.
Most stillbirths occur in full-term pregnancies
 Mermaid
Syndrome

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 Mermaid Syndrome (sirenomillia)
96

 1: 100,000. It is not a mitos.

 is usually fatal within a day or two of birth because of
complications associated with abnormal kidney and
urinary bladder development and function.
 It results from a failure of normal vascular supply
from the lower aorta in utero.
 Maternal diabetes has been associated with caudal
regression syndrome and sirenomelia,[3] although a
few sources question this association
 Menopause & Aging

Menopause → cessation of reproductive cycles.

Why? Due to ovary which unable to respond to
gonadotrophins. --- absence of negative feedback leads to
increase of gonadotrophins.
Estrogen absence leads to some symptoms:
- Hot flashes, osteoporosis.

What about male?

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