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PHYSIOLOGY OF

REPRODUCTION
A. P. Soibi-Harry

Introduction
Sexual reproduction requires a male and a female of
the same species to copulate and combine their
genes in order to produce a new individual who is
genetically different from his parents .
The male reproductive system produces , sustains ,
and delivers sperm cells (spermatozoa) to the female
reproductive tract .
The female reproductive system produces , sustains ,
and allows egg cells (oocytes ) to be fertilized by
sperm It also supports the development of an
offspring (gestation) and gives birth to a new
individual (parturition) .

The Cycle Of Live

GENDER
DETERMINATION

Internal Sex Organs- Effects of SRY

External Sex organs- Indirect


effects of SRY

Male Reproductive System

STRUCTURE
PENIS

SCROTUM

FUNCTION
- A copulatory organ that is responsible for delivering the
sperm to the female reproductive tract.
- Contains 2 erectile tissues called corpus cavernosa and
corpus spongiosum. Urethra passes through penis
- Pouch of skin and muscle that contains the testes.
- Regulates temperature at slightly below body
temperature.

EPIDIDYMIS

- Tightly coiled duct lying just outside each testis


connecting to vas deferens where sperm is stored (for
about 3 days) , matured and become fully functional.
- Contains cilia on its columnar epithelium that help move
sperm toward vas deferens during ejaculation.

TESTES

- Produces sperm via spermatogenesis and the male sex


hormone (testosterone).
- Developed in a male fetus near the kidneys and descend
to the scrotum about 2 months before birth.
- Each testis contains about 250 functional units called
lobules ; each lobule contains about 4 seminiferous
tubules where spermatogenesis occurs.

STRUCTURE

FUNCTION

URETHRA

- A tubule located inside the penis for urine excretion


and semen ejaculation.
- Contains smooth muscle that performs rapid peristalsis
during ejaculation.

VAS DEFERENS - Muscular tubes connecting testis to urethra. Each tube


is about 30 cm long.
- Sperm are transferred from the vas deferens into the
urethra.
SEMINAL
VESICLE

- Secretes an alkaline solution that makes up 60% of the


semen volume ; this seminal fluid contains fructose
(nutrient for the sperm) and prostaglandins ( that
stimulate uterine contraction during sexual excitation).

PROSTATE
GLAND

- Secretes a slightly acidic , milky white fluid that makes


up about 30% of semen volume ; this fluid helps
neutralize the pH of semen and vaginal secretion.

BULBOURETHR - Secretes a clear lubricating fluid that aids in sexual


AL GLAND
intercourse.

Male Gonad- Testis

Testis
Basic functional unit- about 250 Lobules with each lobule
having approximately 4 seminiferous tubules.
Seminiferous tubule functions to:
Produce, maintain, and store the sperm.
Produce hormones/paracrines
Sertoli cells:
Separate the lumen from the basal lamina and create
a blood-testis barrier.
Lumen low glucose, high K+ & steroid hormones
Basal compartment the baso-lateral side of the
sertoli cells &
containing the developing spermatogonia
Interstitial fluid space below the basal lamina and
contains the Leydig cells

Sertoli cells Contd


Produce hormones & paracrines
Anti-Mllerian Hormone (AMH)
Secreted during embryogenesis
Prevents development of the Mllerian ducts
Inhibin & activin
Regulate FSH release from anterior pituitary
inhibin decreases FSH release
activin increases LH function & increases FSH release
Androgen Binding Protein (ABP)
Binds to testosterone and DHT, reduces the loses due to diffusion
resulting in an increase in testicular testosterone levels
Estradiols & Aromatase
Support spermatogenesis
GDNF (glial derived neurotrophic factor) & ERM transcription
factor
Maintenance of the stem cell line

Leydig cells
Produce androgens:
Testosterone,
Androstenedione
Dehydroepiandrosterone (DHEA)
Increase spermatogenesis
Influence secondary sexual characteristics

Hormonal Control Of Male


Reproductive Functions

The Brain Testicular Axis

Control Of The Testes


GnRH secreting neuroendocrine cells in the hypothalamus
fire a brief burst of action potentials approx. every 90min,
secreting GnRH at these times.
The GnRH reaching the anterior pituitary gland via the
hypothalamo-pituitary portal vessels during each periodic
pulse triggers the release of both LH and FSH.
FSH acts primarily on the Sertoli cells to stimulate the secretion
of paracrine agents required for spermatogenesis.
LH acts primarily on the Leydig cells to stimulate testosterone
secretion.

The testosterone secreted by the Leydig cells also acts


locally, in a paracrine manner by diffusing from the
interstitial spaces into the seminiferous tubules. It enters
the Sertoli cells, where it facilitates spermatogenesis

Control Of The Testis Contd


Though FSH and LH are produced by the same cell type, their
secretion rates can be altered to different degrees by negative
feedback inputs.
Testosterone inhibits LH secretion in two ways:
It acts on the hypothalamus to decrease amplitude of GnRH bursts,
which result in a decrease in gonadotropins
It acts directly on the anterior pituitary gland to decrease the LH
response to any given amount of GnRH.

FSH stimulates Sertoli cells to increase both spermatogenesis


and inhibin production, and inhibin decreases FSH release, this
is a logical completion of a negative feedback loop.
Despite all these complexities the total amounts of GnRH, LH,
FSH, testosterone and inhibin secreted and sperm produced do
not change dramatically from day to day.

Testosterone
Effects of Testosterone in the Male
1.Required for initiation and maintenance of spermatogenesis(acts via
Sertoli cells)
2.Decreases GnRH secretion via an action on the hypothalamus
3.Inhibits LH secretion via a direct action on the anterior pituitary
gland
4.Induces differentiation of male accessory reproductive organs and
maintain their function
5.Induces male secondary sex characteristics; opposes action of
estrogen on breast growth
6. Stimulates protein anabolism, bone growth and cessation of bone
growth
7. Required for sex drive and may enhance aggressive behaviour
8. Stimulates erythropoietin secretion by the kidneys

Sperm Cell

DEVELOPMENTAL STAGES OF SPERM

FETAL
LIFE

PRIMORDIAL GERM CELL = Migrates


& diff
SPERMATOGONIUM = Mitosis

PRIMARY SPERMATOCYTE = Meosis I


PUBERT SECONDARY SPERMATOCYTE =
Y
Meosis II
Life
long!

SPERMATID = Spermiogenesis
SPERM = Ready to go!
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Spermatogenesis
Spermatogenesisis the process in
which spermatozoa are produced
from male primordial germ cells by
way of mitosis and meiosis.
The initial cells in this pathway are
called spermatogonia, which yield
primary spermatocytes by mitosis.

Spermatogenesis
Each of four spermatids
develop into a sperm
Second meiosis division
give four spermatids,each
with 23 single stranded
chromosomes
First meiosis division give
two secondary
spermatocytes, each with
23 chromosomes that
become double stranded.
Primary spermatocyte with
2n=46 chromosomes
Spermatogonium with
2n=46 chromosomes
multiply by mitosis.

Spermiogenesis and Sperm


structure
.

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Spermiogenesis
The Golgi vesicles combine to form an acrosomal vesicle full
of enzymes that lies over the nucleus.
The nucleus condenses in size and is stabilized by special
proteins called protamine
Centrosomes start to organize microtubules into long flagella.
Mitochondria start to localize next to the flagella to provide
ready energy.
Sperm are tiny, but highly specialized missiles for delivering
the male genome:

Points to Emphasize
In the fetus, primordial germ cells enter the testes and differentiate
into spermatogonia, immature cells that remain dormant until puberty
Sperm production begins at puberty and continues throughout the life
of a male (contrast female).
The entire process beginning with a primary spermatocyte, takes
about 74 days (70-80) and four functional sperms develop from each
primary spermatocyte.
After ejaculation, the sperm can live for about 48 hours in the female
reproductive tract.
Capacitation is the biochemical removal of sperm surface glycoprotein
that initiates whip lash movement of the sperm tail & occurs in uterus
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The sexual response-Erection Reflex Pathway

Female External Genitalia

Female Reproductive System

The Ovary
Primary female reproductive organ or gonads.
Each ovary is a solid, ovoid structure
about the size and shape of an almond
about 3.5cmX 2cm X1cm

Location:
Located in shallow depressions, called ovarian fossa,
one on each side of the uterus, in the lateral walls of
the pelvic cavity.
They are held loosely in place by peritoneal
ligaments.
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The Ovary-Structure

The ovaries are covered on the outside by a layer


of simple cuboidal epithelium called germinal
epithelium. Underneath this layer is a dense
connective tissue capsule, the tunica albuginea.
The substance of the ovaries is distinctly divided
into an outer cortex and an inner medulla.
The cortex appears more dense and granular due
to the presence of numerous ovarian follicles in
various stages of development. Each of the follicles
contains an oocyte.

The medulla is loose connective tissue with


abundant blood vessels, lymphatic vessels, and

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Folliculogenesis
2 main phases
- Preantral not dependent on FSH
- Antral (Graffian) dependent on FSH

2-cell, 2-gonadotrophin hypothesis for estrogen


production:
Theca cells in response to LH produce androgens which are then converted
to estrogen in granulosa cells by aromatization that is FSH-induced.
Granulosa cells are dependent on androgens from theca cells to make
estrogen
Theca cells secret androgens and progesterone but have only LH receptors.
Granulosa cells secret estrogens and progesterone and has FSH and LH
receptors (has aromatase enzyme)
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Oogenesis

Oogenesis 1

The sequence of events in oogenesis is similar to


the sequence in spermatogenesis but the timing
and final result are different.
Early in fetal development, primitive germ cells in
the ovaries differentiate into oogonia. These divide
rapidly to form thousands of cells, still called
oogonia, which have a full complement of 46 (23
pairs) chromosomes.
Oogonia then enter a growth phase, enlarge, and
become primary oocytes.
The diploid(46 chromosomes) primary oocytes
replicate their DNA and begin the first meiotic

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Oogenesis 2

At birth, the two ovaries together contain approximately


700,000- 2million oocytes.

By puberty, the number of primary oocytes further declines to


about 400,000.

In a womans live time only about 400 to 500 will be ovulated.

Beginning at puberty, under the influence of FSH, several


primary oocytes start to grow. The follicular cells become
cuboidal, the primary oocyte enlarges, and it is now a primary
follicle. The follicular cells proliferate to form several layers of
granulosa cells around the primary oocyte.

Most of these primary follicles degenerate along with the primary


oocytes within them, but usually one continues to develop each
month.
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Oogenesis 3

The large cell undergoes an unequal division so that nearly all


the cytoplasm, organelles, and half the chromosomes go to one
cell, which becomes a secondary oocyte. The remaining half of
the chromosomes go to a smaller cell - first polar body.

Secondary oocyte begins the 2nd meiotic division, but the


process stops in metaphase, at the point of ovulation.

If fertilization occurs, meiosis II continues. Again this is an


unequal division with all of the cytoplasm going to the ovum,
which has 23 single-stranded chromosomes. The smaller cell
from this division is termed second polar body.

The first polar body also divides in meiosis I to produce two


even smaller polar bodies. If no fertilization, the 2nd meiotic
division is never completed & the secondary oocyte
degenerates.
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Ovary showing various stages in the life of a Graafian follicle:


Ovarian Cycle (1) Follicular phase; (2) Ovulation; (3) Luteal
phase

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Post Ovulation
After ovulation and in response to luteinizing hormone, the
portion of the follicle that remains in the ovary enlarges
and is transformed into a corpus luteum.
The corpus luteum secretes progesterone and some
estrogens. Its fate depends on whether fertilization occurs.
If fertilization does not take place, the corpus luteum
remains functional for about 10 days then it begins to
degenerate into a corpus albicans, which is primarily scar
tissue, and its hormone output ceases.
If fertilization occurs, the corpus luteum persists and
continues its hormone functions until the placenta develops
sufficiently to secrete the necessary hormones. Again, the
corpus luteum ultimately degenerates into corpus albicans,
but it remains functional for a longer period of time.
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Uterus

Uterus
The uterus is a hollow, pear shaped muscular organ.
The uterus measures about 7.5cm X 5cm X 2.5cm
about 50 60 gm in weight
Normal position is anteverted (rotated forward)
slightly anteflexed (flexed forward)
The uterus divided into three parts:
-Body
-Isthmus
-Cervix

The Menstrual Cycle

Themenstrual cycleis a complex series of physiological


changesoccurringin women on a monthly basis. It results in
production of an ovum and thickening of the endometrium to
allow for implantation if fertilization should occur.

It is orchestrated by the endocrine system through the complex


interaction of the hypothalamus,pituitaryand ovaries.

The entire cycle lasts about 28-30 days, with the cycle beginning
on the first day of menstruation & ovulation occurring on day 14
or day 16.
The ovarian cycle
Development of ovarian follicle
Production of hormones
Release of ovum during ovulation
The uterine cycle
Removal of endometrium from prior uterine cycle
Preparation for implantation of embryo under the influence
of ovarian hormones

The Cycles Contd


Three Phases of the Ovarian Cycle
Follicular phase
Ovulatory phase
Luteal phase

Three Phases of the Uterine Cycle


Menses
Proliferative Phase
Secretory Phase

These ovarian and uterine phases are


intimately linked together by the
production and release of hormones

Hormonal Control Of The


Ovarian Cycle

Hormonal Control Of The Ovarian Cycle 2

The hypothalamus produces Gonadotropin Releasing


Hormone(GnRH) in a pulsatile manner which binds to the
pituitary stimulating release of Luteinizing hormone(LH) and
Follicle StimulatingHormone(FSH)

FSH binds to the granulosa cells of the ovaries stimulating;


Development of ovarian follicles
Secretion of estrogen
Secretion of inhibin
(The follicle most sensitive to FSH becomes dominant and is
known as the Graafian follicle)

LH binds to the theca cells of the ovaries causing;


Production of estrogen which is required for ovulation and
thickening of the endometrium
Conversion of the Graafianfollicleinto the progesterone
producing corpusluteum

Follicular Phase
At the start of the cycle levels of FSH rise causing growth and
development of a few ovarian follicles, as follicles mature
they compete with each other for dominance. The 1st follicle
to become fully mature produces large amounts of estrogen
which inhibits the growth of the other competing follicles. The
dominant follicle called the Graafian follicle continues to
secrete increasing amounts of estrogen.
Estrogen causes;
Endometrial thickening
Thinning of cervical mucous to allow easier passage of
sperm
Estrogen also initially inhibits LH production from the
pituitary gland, however when the ovum is mature, estrogen
reaches a threshold level which causes a sudden spike in LH
around day 12 of the cycle.

The LH surge and ovulation


The LH surge occurs in response to the rapid rise in estradiol
during the latter days of the follicular phase of the ovarian cycle.
Pulses of GnRH from the hypothalamus increase in both magnitude
and frequency, triggering the LH surge with a rapid outpouring of
LH and, to a lesser extent, FSH from the anterior pituitary. The LH
surge is also preceded by a rise in serum concentration of
progesterone. The contribution of this rise to the peri-ovulatory
phase of the cycle is unclear, but prevention of the pre-ovular rise
in serum progesterone concentration using the progesterone
receptor antagonist mifepristone prevents efficient ovulation.
The LH surge initiates final maturation of the oocyte with
completion of meiosis and extrusion of the first polar body, which
contains one of the two haploid sets of chromosomes from the
oocyte.
The LH surge also induces an inflammatory type reaction at the
apex of the follicle adjacent to the outer surface of the ovarian
cortex.

A process of new blood vessel formation, with


associated release of prostaglandins (PGs) and
cytokines leads to rupture of the follicle wall and
ovulation about 38 h after the initiation of the LH
surge.
The empty follicle rapidly fills with blood and the
theca and granulosa cell layers of the follicle wall
luteinize, with formation of the corpus luteum.
Rapid synthesis of progesterone, along with
estradiol, follows. Concentrations of progesterone
in serum rise to above 25 nmol/l.These
concentrations rise still further if pregnancy follows.

Luteal Phase 1
Once ovulation has occurred LH & FSH cause the remaining
Graffian follicle to develop into the corpus luteum which begins
to produce the hormone progesterone
Progesterone causes;

Endometrium becoming receptive to implantation of the


blastocyst

Increased production of estrogen by the adrenal glands

Negative feedback causing decreased LH & FSH(both


needed to maintain the corpus luteum)

Increase in the womans basal body temperature

Luteal Phase 2
As the levels of FSH & LH fall, the corpus luteum
degenerates and progesterone production ceases. The
falling level of progesterone triggers menstruation &
the entire cycle starts again.
However if an ovum is fertilized it produces hCG which
is similar in function to LH.This prevents degeneration
of the corpusluteum(continued production of
progesterone), thus preventing menstruation.
The placenta eventually takes over the role of the
corpusluteum(from 8 weeks)

Hormonal Regulation Of The Uterine Cycle

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The Uterine Cycle


Theuterine cycle is controlled by cyclical release of hormones from the
ovaries. The endometrium is the part of the uterus most affected by these
changes in hormone levels.
It is composed of 2 layers;
Functional layer this grows thicker in response to estrogen and is shed
during menstruation
Basal layer -this forms the foundation from which the functional layer
develops it is not shed
The uterine cycle has 3 phases known as the proliferative,secretory &
menstrual phases
Proliferative phase
During the proliferative phase the endometrium is exposed to an increase
in estrogen levels caused by FSH & LH stimulating the ovaries.This
estrogen causes repair & growth of the functional endometrial layer
allowing recovery from the recent menstruation & further proliferation of
the endometrium.
Continued exposure to increasing levels of estrogen causes;
Increased endometrial thickness
Increased vascularity -spiral arteries grow into the functional

The Uterine Cycle


Secretory phase
The secretory phase begins once ovulation hasoccurred. It is controlled
by progesterone produced by the corpus luteum and results in the
endometrial glands beginning to secrete various substances which make
the uterus a more welcoming environment for an embryo to implant.
Menstrual phase
At the end of the luteal phase the corpusluteumdegenerates(if no
implantation occurs). The loss of the corpus luteum results in decreased
progesterone production causing the spiral arteries in the functional
endometrium to contract.
The loss of blood supply causes the functional endometrium to become
ischemic and necrotic. As a result the functional endometrium is shed
and passed out through the vagina.
This is seen as the 3-5 day period of menstruation a woman experiences
each month

Window of fertility

A womans most fertile period is between 5


days before ovulation until 1 to 2 days after
Women can therefore use knowledge of
their cycle to improve chances of
conception
Women may also monitor symptoms that
suggest they are about to ovulate such as;
Basal body temperature measuringit spikes during
the LH surge 24-48 hours before ovulation
Thinning of cervical mucous

Female Reproductive Physiology

Fertilization Effects

What happens if fertilization occurs?

Uterine endometrium is maintained by


First the release of progesterone from the corpus luteum,
Then the release of hCG (human chorionic gonadotropin)
which maintains the corpus luteum until the 7th week,

From 7th week on, the placenta produces


Estrogen and Progesterone which at high levels blocks GnRH
Estrogen is also involved in breast development
Progesterone is also involved in uterine maintenance and
relaxation (prevents premature contractions)
Human placental lactogen(hPL)
Implicated in breast development and milk production
Implicated in alteration of maternal glucose and fatty acid
metabolism

Conclusion

Reproduction involves a complex series of


events modulated by the HPO axis in both
males and females.
Knowledge of the physiology of
reproduction will enable us as
obstetricians and gynecologist to render
specialized services to our clients
especially in this age of improving
assisted reproductive technology.

References

Block E (1951) Quantitative morphological investigations


of the follicular system in women. Acta Endocrinol 8, 33.
Groome NP, Illingworth PJ, OBrien M et al. (1996)
Measurement of dimeric inhibin B throughout the human
menstrual cycle. J Clin Endocrinol Metab 81,14015.
Macklon NS & Fauser BCJM (2001) Follicle-stimulating
hormone and advanced follicle development in the
human. Arch Med Res 32, 595600.
Rogers PAW& Gargett CE (1999) Endometrial
angiogenesis. Angiogenesis 2, 28729.

THANKS FOR YOUR


ATTENTION

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