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Between week 1 and 6, female and male embryos
are phenotypically indistinguishable, even though
the genotype (XX or XY) of the embryo is
established at fertilization.
 By week 12, some female and male characteristics
of the external genitalia can be recognized.
 By week 20, phenotypic differentiation is complete.

2
The indifferent gonads develop in a longitudinal
elevation or ridge of intermediate mesoderm called the
urogenital ridge
 Primordial germ cells arise from the lining cells in
the wall of the yolk sac at weeks 3-4.
 At week 4-6, primordial germ cells migrate into the
indifferent gonad.


Male germ cells will colonise the medullary region and the
cortex region will atrophy.

Female germ cells will colonise the cortex of the primordial
gonad so the medullary cords do not develop.
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Spermatogonia → spermatozoa. Spermatogenesis
take about 70 day.
 Germ cells colonise the sex cords in the primordial
gonad.
 These cords connect with the rete testis, the
epididymis and the vas deferens. Before birth, the
germ cells proliferate by mitosis to form
spermatogonia stem cells.
 These begin mitosis to maintain a population of selfregenerating stem cells that remain available up to
and beyond the age of 70, to allow for continuous
sperm production at a high rate.

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At puberty, the cords hollow out to form the
seminiferous tubules, where sperms are
produced. Each testis has 250-750 tubules, which
empty into the rete testis, and from there form the
epididymis.
 Spermatogonia (diploid 2n) (fixed number of
mitotic divisions typically 64) → Primary
Spermatocytes (diploid 4n) … all linked
together by cytoplasm bridges.

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Primary Spermatocytes (push their way towards
the lumen of the tubule ) → meiosis (M)
 M1: two secondary spermatocytes (haploid 2n)
 M2: four Spermatids (haploid 1n)
 Each
Spermatogonium yields up to 256
spermatids.
 Spermatids are re-modelled to form sperm by
Spermiogenesis, and the cytoplasmic bridges
between them are broken down before they are
released into the tubule lumen to be washed down to
the rete testis by fluid secreted from Sertoli cells

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Spermiogenesis
(1) formation of the acrosome, which covers half of the
nuclear surface and contains enzymes to assist in
penetration of the egg and its surrounding layers
during fertilization
(2) condensation of the nucleus;
(3) formation of neck, middle piece, and tail;
(4) shedding of most of the cytoplasm as residual
bodies that are phagocytized by Sertoli cells.
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



Primordial germ cells colonise the cortex of the primordial
gonad, becoming Oogonia.
These proliferate rapidly by mitosis, so by 20 weeks of
gestation there are over 7 million, however most of these die,
leaving about 2 million that all begin meiosis before birth to
become Primary Oocytes.
The Oogonia’s entry into meiosis 1 is stimulated by
Mesonephric cells. These are flattened epithelia cells, also
called Follicular Cells or Granulosa Cells, which surround the
primary oocytes to form Primordial Follicles.
Meiosis is then arrested at the diplotene stage (a resting stage)
of prophase due to Oocyte Maturation Inhibitor (OMI)
secreted from the Follicular Cells.
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A woman therefore has all the oocytes she will
ever have at birth – no more can be formed later
and all ova are produced from this ‘stock’, some of
which may remain arrested for 50 years before
further development.
 However, remaining in this arrested stage for many
years increases the chance of cell damage,
accounting for the increasing risk of foetal
chromosomal abnormalities in pregnancies of older
women.
 Beginning at puberty until the menopause about 40
years later, a small number of follicles (15-20) begin
further development each month.
 Formation of a mature gamete requires the follicle to
go through 3 stages.
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
› The primary oocyte grows dramatically, but does not
re-start meiosis
› Flat follicular cells become cuboidal Granulosa cells
› Granulosa cells secrete glycoprotein to surround the
oocyte with a Zona Pellucida
› Surrounding connective tissue (stroma) cells form a
Theca Folliculi
 Inner Theca Interna that is vascular and endocrine
 Outer Theca Externa that is a fibrous capsule
› Theca and Granulosa cells collaborate to secrete
oestrogens
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› Granulosa cells continue to proliferate and a fluid appears
between them, forming the antrum
› As more fluid forms, this secondary or Graafian follicle
expands
› Expands to 2mm diameter without stimulation from
reproductive hormones
› Continued development depends on reproductive
hormones.
 FSH – Binds only to Granulosa cells
 LH – Binds only to Thecal cells
› Under the influence of LH, Thecal cells secrete androgens,
which are converted to oestrogens by the Granulosa cells
under the influence of FSH
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› Begins 37 hours before ovulation
› Oestrogen causes receptors for LH to appear on outer Granulosa cells
› LH surge stimulates these receptors, leading to rapid changes in the follicle
› Within 3 hours of the LH surge, the follicle restarts meiosis, and the first
›
›
›
›
›
›
meiotic division is completed. This division is asymmetric; cytoplasm
remains with one daughter cell and the other forms a condensed polar body.
The secondary follicle then enters meiosis II and arrests again 3 hours
prior to ovulation.
Follicle size increases dramatically by increase in antral fluid volume to 25mm
diameter
Structure begins to weaken
LH stimulates collagenase activity leading to follicle rupture
Ovum is carried out in the fluid and gathered up into the fallopian tube by
fimbria
Meiosis is not completed unless the ovum is fertilised
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
Pre-ovulatory follicle:
Secondary follicle mature + LH surge → Pre-ovulatory growth
phase:
1.
MI completed → unequal size daughter cells each with 23
chromosomes: secondary
perivetelline space ).
2.
oocyte
and 1st
polar body
(in
Secondary oocyte begin MII but arrested in metaphase about 3
hours before ovulation where MII completed only if oocyte
fertilized.

If oocyte not fertilized → degenerate after about 24 hours.

1st PB also undergo 2nd division (MII).
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The remains of the follicle (granulosa cells and theca interna)
re-organise themselves into a corpus luteum cells, which secretes
progesterone and oestrogen under the influence of LH.
o In humans the corpus luteum lives for 14 days before regressing
spontaneously, in the absence of a fertilization, where it called
corpus albicans.
o If the oocyte is fertilized, degeneration of the corpus luteum is
prevented by human chorionic gonadotropin (hCG), a hormone
secreted by the syncytiotrophoblast of the developing embryo.
o The corpus luteum continues to grow and forms the corpus
luteum of pregnancy (corpus luteum graviditatis).
o
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
By the end of the third month, this structure may be
1/3 to 1/2 of the total size of the ovary.

Luteal cells continue to secrete progesterone until
the end of the fourth month; thereafter, they regress
slowly as secretion of progesterone by the
trophoblastic component of the placenta becomes
adequate for maintenance of pregnancy.

Removal of the corpus luteum of pregnancy before
the fourth month usually leads to abortion.
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
Conception: it is formation of a zygote resulting
from the union of a sperm and egg cell (oocyte)
by the process of fertilisation that take place in
ampullary region of fallopian tube.
Sperm transport through the cervix and uterus
 Immediately after ejaculation in the vagina, the
semen first coagulates due to the action of
clotting factors (fibrinogen). This is to prevent
sperm being physically lost from the vagina. 10 –
20 minutes later the semen re-liquefies by the
action of enzymes found in prostatic secretions.
 The vast majority of sperm do not enter the
cervix of the uterus and are lost by leakage from
the vagina. Those that do enter the uterus have to
travel 15 – 20cmto reach the uterine tube, a
journey that may last a few hours.

Transport of sperm is as a result of their own
propulsive capacity and the fluid currents
caused by the action of ciliated cells in the
uterine tract.
 Capacitation
of sperm and the acrosome
reaction

During their passage through the uterus to the
uterine tube, sperm undergo a series of
maturational changes, Capacitation and the
Acrosomal Reaction. Both capacitation and the
acrosomal reaction are induced by an influx of
calcium and a rise in cAMP in spermatozoa.
Capacitation
 Further maturation of sperm in female
reproductive tract (6 – 8 hours)
 Sperm cell membrane changes to allow fusion
with oocyte cell surface
› Removal of glycoprotein coat

Tail movement changes
› Beat  Whip-like action

Sperm become responsive to signals from the
oocyte
Acrosomal Reaction
 Capacitated sperm comes into contact with the
oocyte zonapellucida
 Membranes fuse Start of reaction
 Acrosome swells and liberates its contents by
exocytosis
 Proteolytic enzymes and further binding facilitate
penetration of the zonapellucida by the sperm
(takes about 15 minutes)

Mechanisms involved in fertilisation of the ovum
By the time of ovulation, the ovum (primary
oocyte) in the ovulatory follicle has completed its
first meiotic division to form a secondary oocyte.
 Secondary Oocyte

› Haploid number of chromosomes and bulk of
cytoplasm

First Polar Body
› Remaining haploid number of chromosomes

The secondary oocyte, surrounded by follicular
cells (cumulus) embedded in a gelatinous matrix, is
released from an ovulatory follicle and picked up
by the fimbria of the uterine tube and guided into
its lumen by the ciliary movements of epithelial
cells towards the ampulla, the site of fertilisation,
where the oocyte and sperms come together.
Only one sperm penetrates the cytoplasm of the
ovum and its nucleus fuses with the nucleus of the
ovum. This forms the zygote. Sperm entry to oocyte
will cause:
1.Cortical and zona reaction so oocyte become imper
meable to further sperm preventing polyspermia.
2. Resumption of second meiotic division.
3. Metabolic activation of oocyte.

So the main results of fertilization are:
1.Restoration of the diploid number of
chromosome.
2.Determination of sex of new individual.
3. Intiation of cleavage.
 Within
a few hours the zygote begins to divide
by a series of mitotic cell divisions known as
cleavage to form a ball of cells called the
morula and then a hollow structure, the
blastocyst. During this transformation process
it is gradually transported along the uterine
tube towards the uterus.

By the time the blastocyst enters the uterine cavity
(4 – 5 days after fertilisation), the endometrium is
ready to receive it for pregnancy to be established.
After a day or so in the uterine cavity the
blastocyst attaches itself to the uterine
endometrium – implantation.