Ovarian Cycle

During each ovarian cycle,

up to 20 primordial
follicles are activated to
begin the maturation
process, but usually only
one reaches full maturity,
the remainder regress
(Figure 4).
The ovarian cycle can be
divided into 3 phases:.
1. Follicular phase
From many
primordial follicles
one Graafian
follicle develops.
2. Ovulatory phase
The graafian
follicle is released.

The ovarian cycle (Figure 4)

3. Luteal phase
The corpus luteum
and corpus
albicans are
produced.
1. Follicular Phase
Follicular development from the primordial follicles is as follows (Figure 4):
1. Primary follicle stage:
Follicular epithelium surrounding the oocyte thickens to form cuboidal granulosa cells,
Zona pellucida forms between the oocyte and granulosa cells.
2. Growing follicle stage:
Granulosa cells proliferate forming a multi layered capsule around the oocyte. Most
growing follicles regress and die.
3. Antral (or secondary follicle) stage:
Remaining follicles take up fluid and develop a central cavity (antrum). Connective tissue
surrounding the follicles forms 2 layers, an inner theca interna and an outer theca externa.
Cells of the theca interna secrete oestrogen. Usually, only one antral follicle becomes
dominant and enlarges. The rest degenerate (atresia).

4. Graafian follicle stage:

The first meiotic division is completed just before ovulation. The oocyte is now known as
the secondary oocyte and commences its 2nd meiosis. The antrum enlarges. The
granulosa cells around the secondary oocyte settle at the edge of the antrum as the
cumulus oopherus. The follicle is now 1.5 - 2.5 cm in diameter.
2. Ovulatory Phase
Once fully developed the Graafian follicle bulges from the external wall of the ovary. Ovulation
occurs when the ovarian wall ruptures and expels the secondary oocyte into the peritoneal cavity.
The second meiotic division of the oocyte is completed only after penetration of the oocyte
(known as an ovum) by a spermatozoon.
3. Luteal Phase
After ovulation, the granulosa cells of the graafian follicle proliferate and form the corpus luteum
which is highly vascularised and secretes progesterone and estrogens.
Progesterone, from the corpus luteum prepares the endometrium for implantation (see menstrual
cycle). If fertilisation does not occur and an ovum does not implant into the uterine wall, the
corpus luteum degenerates and forms the corpus albicans.
If implantation does occur, the developing placenta secretes human chorionic gonadotrophin
(HCG) which prevents degeneration of the corpus luteum and prolongs secretion of
progesterone. After 5-6 weeks the placenta is sufficiently developed and takes over as the main
organ of progesterone secretion.

Hormonal Control of the Ovarian Cycle (Figure 5)

During the ovarian cycle, growth and development of the follicle is driven by two gonadotrophic
hormones:
1. Follicle Stimulating Hormone (FSH)
2. Luteinising hormone (LH)
Both FSH and LH are secreted by the anterior pituitary and are under the control of
gonadotrophin releasing hormone (GnRH) secreted by the hypothalamus.
FSH and LH stimulate follicle growth. As the follicle grows, thecal cells secrete estrogens.
Rising levels of estrogen in the plasma have a negative feedback effect on the anterior pituitary
inhibiting output of FSH and LH.
However, this negative feedback is only transient and as levels of estrogen increase they begin to
have a positive effect on the hypothalamic-pituitary axis resulting in a burst of LH and, to a
lesser extent, FSH.
This sudden burst of LH and FSH stimulates completion of meiosis I in the primary oocyte and
is also believed to be involved in stimulating synthesis of enzymes involved in bulging of the
ovarian wall.

After ovulation, LH promotes the transformation of the ruptured graafian follicle into the corpus
luteum. LH stimulates the corpus luteum to secrete progesterone and estrogen.
Progesterone and estrogen from the corpus luteum have a negative feedback effect on the
anterior pituitary and inhibit FSH and LH production. This prevents development of new
follicles.
As LH levels fall, the corpus luteum begins to degenerate. Levels of progesterone and estrogen
fall. FSH and LH are again produced by the anterior pituitary and a new cycle begins.
Menstrual Cycle
The uterine or menstrual cycle is a
series of cyclic changes in the
endometrium that occur on a
monthly basis in response to
changes in levels of ovarian
hormones.
Three phases of the menstrual cycle
are recognised. These correlate
with the ovarian cycle such that the
endometrium is most receptive to
implantation of the fertilised oocyte
7 days after ovulation.
Menstrual phase (1-5 days)
The functional layer of the
endometrium becomes detached
from the uterine wall and this
results in bleeding. Blood loss is
usually between 50-150ml.
Detached tissues and blood pass
through the vagina as the menstrual
flow.
Proliferative phase (days 6-14)
As levels of estrogen increase the
endometrium begins to proliferate
and thicken, tubular glands and
spiral arteries form. Estrogen also
stimulates the synthesis of
progesterone receptors in
endometrial cells. Ovulation occurs

The menstrual cycle and its relation to the ovarian cycle

(Figure 6)
at the end of this phase.
Secretory phase (days 15-28)
Rising levels of progesterone
produced by the corpus luteum act
on the endometrium stimulating the
enlargement of glands which begin
secreting mucus and glycogen in
preparation for implantation of the
fertilised ovum.
If fertilisation does not occur, the
corpus luteum degenerates,
progesterone levels fall and the
endometrium degenerates. The
cycle starts again with the first day
of menstrual flow.

Photomicrograph 11, Ovary

Photomicrograph 12, Growing Follicle

Photomicrograph 13, High power of Graafian Follicle

Copulation and Fertilization

For fertilization to occur, sperm must be deposited in the vagina within a few days before or a
day or two after ovulation. Sperm transfer is accomplished by copulation. Sexual excitation
dilates the arterioles supplying blood to the penis. Blood accumulates in three cylindrical spongy
sinuses that run lengthwise through the penis. The resulting pressure causes the penis to enlarge
and erect and thus able to penetrate the vagina.
Movement of the penis back and forth within the vagina causes sexual tension to increase to the
point of ejaculation. Contraction of the walls of each vas deferens propels the sperm along.
Fluid is added to the sperm by the seminal vesicles, Cowper's glands, and the prostate gland.
These fluids provide
a source of energy (fructose)
an alkaline environment to activate the sperm, and

Perhaps in other ways provide an optimum chemical environment for them.

The mixture of sperm and accessory fluids is called semen. It passes through the urethra and is
expelled into the vagina.
Physiological changes occur in the female as well as the male in response to sexual excitement,
although these are not as readily apparent. In contrast to the male, however, such responses are
not a prerequisite for copulation and fertilization to occur.

Once deposited within the vagina, the sperm proceed on their journey into and through the uterus
and on up into the fallopian tubes. It is here that fertilization may occur if a secondary oocyte in
metaphase of meiosis II.
Although sperm can swim several millimeters each second, their trip to and through the fallopian
tubes may be assisted by muscular contraction of the walls of the uterus and the tubes. There is
also evidence that they respond to a chemical attractant produced by the egg or the tissues
surrounding it. Sperm may reach the egg within 15 minutes of ejaculation. The trip is also
fraught with heavy mortality. An average human ejaculate contains over one hundred million
sperm, but only a few dozen complete the journey. And of these, only one will succeed in
fertilizing the egg.
Fertilization begins with the binding of a sperm head to the outer coating of the egg (called the
zona pellucida). Exocytosis of the acrosome at the tip of the sperm head releases enzymes that
digest a path through the zona and enable the sperm head to bind to the plasma membrane of the
egg. Fusion of their respective membranes allows the entire contents of the sperm to be drawn
into the cytosol of the egg. (Even though the sperm's mitochondria enter the egg, they are almost
always destroyed and do not contribute their genes to the embryo. Human mitochondrial DNA is
almost always inherited from mothers only.) Within moments, enzymes released from the egg
cytosol act on the zona making it impermeable to the other sperm that arrive.

Secondary oocyte

1. Corona radiata
2. Spindle
3. Zona pellucida
4. Sperm

The expelled secondary oocyte is surrounded by the zona pellucida and several
layers of the follicular cells arranged as the corona radiata.
Fertilization, the process by which the male and female gametes fuse, marks the
Male gametes are produced during the spermatogenesis and stored in the
beginning of the pregnancy. It lasts 24 hours and occurs in the ampullary region of
epididymis. Upon ejaculation into the female genital tract, the spermatozoa are not
the uterine tube. The first event is the scattering of the corona radiata cells by the
capable of fertilizing the oocyte. They must undergo a capacitation period that
released contents of the acrosomal vesicle (hyaluronidase), tubal mucosa enzymes
lasts approximately 7 hours, during which the glycoprotein coat and seminal
and sperm tail movements. Penetration of the zona pellucida is enabled by the
proteins are removed from the surface of the sperm acrosome by the action of the
action of other enzymes released from the acrosome. When the first sperm passes
substances secreted by uterus or uterine tubes. When capacitated spermatozoa
through the zona pellucida, cortical granules are released into the perivitelline space
come into contact with the corona radiata surrounding the secondary oocyte, they
and make the zona pellucida impermeable to other sperms. This mechanism
undergo the acrosomal reaction. This process includes release of the acrosomal
ensures that each oocyte is fertilized by only one sperm. other sperm that arrive.
vesicles content that helps the sperm digest its way to the oocyte plasma
membrane in order to fuse with it.
Fusion of the pronuclei
Mature ovum

1. Fusion of pronuclei
2. Perivitelline space
3. Zona pellucida
1. Perivitelline space
4. Polar bodies
2. Zona pellucida
3. Polar bodies
4. Sperm

When the sperm enters the oocyte, it leaves its plasma membrane behind. After the
sperm entry, the secondary oocyte finishes its second meiotic division, forming an
ovum and a second polar body. The nucleus of the mature oocyte is known as the
female pronucleus. Male pronucleus is formed by the enlarging of the nucleus in
the head of the sperm. During the growth of the pronuclei they replicate their DNA.
At this stage, male and female pronuclei are indistinguishable. Fertilization ends with
the fusion of female and male pronucleus and formation of the zygote. Within 24-48
hours after fertilization, early pregnancy factor (EPF) can be detected in the
maternal serum.

Zygote
1. Zygote
2. Perivitelline space
3. Zona pellucida
4. Polar bodies

Pregnancy

Development begins while the fertilized egg is still within the fallopian tube. Repeated mitotic
divisions produce a solid ball of cells called a morula. Further mitosis and some migration of
cells converts this into a hollow ball of cells called the blastocyst. Approximately one week after
fertilization, the blastocyst embeds itself in the thickened wall of the uterus, a process called
implantation, and pregnancy is established.

The blastocyst produces two major divisions of cells:

Three or four blastocyst cells develop into the inner cell
mass, which will form
o 3 extra embryonic membranes: amnion, yolk sac,
and (a vestigial) allantois and
o

in about 2 months, become the fetus and,

ultimately, the baby.

The remaining 100 or so cells form the trophoblast, which will develop into the chorion
that will go on to make up most of the placenta. All the extra embryonic membranes play
vital roles during development but will be discarded at the time of birth.

The placenta grows tightly fused to the wall of the uterus. Its blood vessels, supplied by the fetal
heart, are literally bathed in the mother's blood. Although there is normally no mixing of the two
blood supplies, the placenta does facilitate the transfer of a variety of materials between the fetus
and the mother.

receiving food
receiving oxygen and discharging carbon dioxide

discharging urea and other wastes

receiving antibodies (chiefly of the IgG class). These remain for weeks after birth,
protecting the baby from the diseases to which the mother is immune.

Act as an endocrine organ producing a number of hormones

Protective barrier - prevents the passage of most pathogens. Some viruses are small
enough to cross the placenta e.g. virus that causes rubella or German measles, and HIV.

endocrine role of the placenta

Hormones secreted by the placenta and their functions.

Oestrogen
1. stimulates growth of the uterus
2. sensitises the uterus to oxytocin
3. stimulates the duct system of the breast
4. Inhibits FSH
5. Inhibits the release of prolactin, therefore inhibits lactqtion9secretion of
milk). Some prolactin is synthesised before birth but released by the
pituitary gland before birth: it stimulates milk secretion.

Progesterone
1. Maintains the uterine lining (the endometrium)
2. Relaxes the muscle of the uterus thus preventing a miscarriage
3. Stimulates the development of milk glands in the breast ready for lactation.
4. Inhibits FSH
5. Inhibits release of prolactin
Human placental lactogen (HPL)
Synthesis increases gradually during pregnancy
Stimulates the development of the breast in preparation for lactation. It is
needed for oestrogen and progesterone to be effective.
Adjusts glucose and fat metabolism of mother to the advantage of the fetus.
Human Chorionic Gonadotrophin (HCG)
1. Produced from the chorion from the time the embryo implants. Target is the
ovary. Maintains the corpus luteum up tot about 3 months, thus maintaining
the production of oestrogen and progesterone until the placenta takes over
this function. Level then declines.

Although the main function of the placenta is to transport nutrients, gases and waste products
between the mother and the foetus the placenta also produces a range of hormones.

The metabolic activity of the placenta is almost as great as that of the fetus itself.
The umbilical cord connects the fetus to the placenta. It receives deoxygenated blood from the
iliac arteries of the fetus and returns oxygenated blood to the liver and on to the inferior vena
cava.

Because its lungs are not

functioning, circulation in the fetus
differs dramatically from that of
the baby after birth. While within
the uterus, blood pumped by the
right ventricle bypasses the lungs
by flowing through the foramen
ovale and the ductus arteriosus.
Although the blood in the placenta
is in close contact with the
mother's blood in the uterus,
intermingling of their blood does
not normally occur. However,
some of the blood cells of the fetus
usually do get into the mother's
circulation where they have
been know to survive for decades.
Far rarer is the leakage of mother's
blood cells into the fetus. However,
it does occur. A few pregnant women with leukemia or lymphoma have transferred the
malignancy to their fetus. Some babies have also acquired melanoma from the transplacental
passage of these highly-malignant cells from their mother.
During the first 2 months of pregnancy, the basic structure of the baby is being formed. This
involves cell division, cell migration, and the differentiation of cells into the many types found in
the baby. During this period, the developing baby called an embryo is very sensitive to
anything that interferes with the steps involved. Virus infection of the mother, e.g., by rubella
("German measles") virus or exposure to certain chemicals may cause malformations in the
developing embryo.

Revision
Sexual Reproduction Involves The
Production And Transfer Of Gametes And
The Achievement Of Fertilisation
Gametes and Gamete Formation
Histology of the Testis

Testes in the scrotal sac (extension of abdominal cavity)

Produce sperm and male sex hormones

Have a constant temp "body temp - 5C" maintained by)

Heat exchange system in arteries and veins

Semi-external position

Muscles in scrotal sac move testes up/down against warmer abdomen

Sterility if testes do not descend during development

Spermatogenesis occurs in walls of seminiferous tubules (compartment of testes)

Sperm are passively carried to the epididymis

o

Network of seminiferous tubules leads into vas deferens

Sperm acquire ability to swim and are stored

Urethra (joining of vas deferens) carries fluids from the urinary and reproductive system

During interaction / pressure in erectile tissue rises / arteries supplying it dilate and veins draining
it constrict

Not discharged sperm are degenerated, absorbed, lost via urine

Histology of the Ovary

Ovaries in the abdominal cavity produce gametes + sex hormones

Stroma within the ovary contains blood vessels

Supply of oxygen and nutrients

Removal of waste products CO2

Transports hormones which control process of reproduction

Follicle development occurs within the ovary

o

Each follicle consists of follicle cells surrounding an oocyte (developing egg)

At birth 1 million primary follicles in each ovary

Remain in suspension until puberty at puberty, only 400k are present

400 will be released into the oviduct during reproductive life of a female

At month intervals 20-25 follicles begin to develop further, from these only a single oocyte is
released

Gametogenesis (Formation of Gametes)

SAME in both sexes a) spermatogenesis, b) oogenesis
1. Multiplication of diploid cells by MITOSIS
a. Epithelium of seminiferous tubules multiplies Daughter cells are pushed towards lumen of
tubule
b. Epithelial cell inside ovary of female fetus multiplies
2. GROWTH of daughter cells from mitotic divisions
3. Products of the growth phase divide by MEIOSIS producing haploid cells (4623)
4. MATURATION of haploid daughter cells into gametes (eggs, sperm)
a. Heads are embedded in Sertoil cells

Prevent destruction of sperm by immune system

Sperm and body cells are genetically different

Provide nutrients Tails are projected into fluid-filled lumen

How gametogenesis differs in females

"b) Unequal cell division in meiosis / 1 ovum and tiny polar bodies produced

b) Primary oocytes form before birth / growth phase before birth

b) Pause in meiosis at prophase I / further development suspended until puberty

b) Pause in meiosis at metaphase II / meiosis not complete until fertilisation occurs" 1

Follicle Development/Ovarian Cycle

Follicular stage [days1-13]

1. Anterior pituitary gland is secreting follicle-stimulating hormone FSH

2. FSH travels in bloodstream to ovary
3. Stimulates development (division) of follicle cells surrounding oocyte
4. Developing follicle cells secrete oestrogen
5. Stimulates proliferation of endometrium and its blood supply
6. Inhibits further secretion of FSH by negative feedback
7. Stimulates anterior pituitary gland to secrete luteinising hormone LH
8. LH brings about ovulation
Ovulation [day14]
// Mature ovarian follicle 15mm in diameter
9. Mature ovarian follicle bursts and releases secondary oocyte (now called ovum!)
10. Corpus luteum forms from remaining follicle cells in ovary
11. Ovum passes down fallopian tube/oviduct towards uterus; fertilization now possible
a. Happens once a month, menstrual cycle 28days
b. Each ovary alternatively releases an ovum every 56days (56/2)
Luteal phase [days15-28]
12. Corpus luteum secretes sex hormones
13. Progesterone continues to stimulate
a. Profileration of endometrium and its blood supply
b. Development of nutrient fluid glands in uterus lining
2. High levels of sex hormones inhibit secretion of LSH and LH
IF FERTILISATION DOES NOT OCCUR

3. Corpus luteum degenerates \ levels of sex hormones fall

4. Uterus lining breaks down; FSH is not inhibited anymore cycle starts again

Uterine Cycle

Menstruation [days1-5] Endometrium breaks down

o

uterus lining/endometrium to disintegrate

its blood vessels to rupture

Flow of blood (menses) passes out of the vagina

Proliferative phase [days6-13] Endometrium rebuilds

o

Low levels of female sex hormones causes

Increased production of oestrogen by ovarian follicle

Secretory phase [days15-28] Endometrium thickens and glands are secretory

Structure of a Mature Sperm Cell

Head: acrosome (enlarged lysosome digestive enzymes penetrate egg), nucleus (n)

Middle piece: mitochondria, ATP needed for tail movement

Tail: flagellum, movement

Movement of Sperm in the Female Reproductive Tract

Sperm are ejaculated into the vagina / deposited outside the cervix
o

Alkalinity of semen neutralises acidic pH in vagina

Mucus allows sperm to swim through cervix / mucus is thin and watery during ovulation /
glycoprotein chains run parallel

Wall of uterus has two distinct layers

o

Bulk of uterus wall consists of myometrium (smooth muscle) / expels fetus at birth

Active muscular contractions during intercourse support sperm

Travel to oviduct in 5hours / survival rate of sperm 48hours

Endometrium is concerned with anchorage and nourishment of embryo

Sperm undergo capacitation while travelling

o

Acquire ability to fertilise 2 oocyte by removal of acrosome membrane proteins

Takes 6hours

Fertilisation occurs in the fallopian tube

o

Walls are lined with ciliated epithelia and contain smooth muscles

Egg moves to uterus via cilia movement and peristaltic muscle contraction

Contact between sperm and oocyte is by chance

Structure of the Egg

0.1mm (100um) in diameter. Sperm's head is only 2.5um across

Haploid nucleus is surrounded by cytoplasm / with enzymes and organelles

Yolk droplets contain proteins and lipids

Outside plasma membrane is a glycoprotein coat called a jelly coat

Acrosome Reaction and Penetration of the Oocyte Membrane

Acrosome reaction
1. Contact of jelly coat and sperm
2. Triggers Ca2+ to enter membrane of sperm
3. Causes acrosome to burst / releases enzymes / digest jelly coat

// enzymes: hyluronidase + acrosin

4. Sperm filament attaches to receptor on vitelline membrane

5. Sperm and egg plasma membranes fuse
6. Sperm nucleus enters egg, tail and middle piece remain outside

Depolarisation of membrane / blocks entry of more sperm

2 oocyte undergoes 2nd division of meiosis / produces ovum + second polar body

Nuclei (ovum + sperm) fuse forming a zygote

Female Infertility

Pituitary gland fails to produce FSH and prevents ovulation

Injections of FSH

TREATMENT:

SIDE EFFECTS:

May produce several eggs at the same time (twins)

Too much oestrogen is secreted which inhibits FSH secretion

o

TREATMENT:

non-steroidal drugs (e.g. clomiphene) which oppose action of oestrogen

Male Infertility

Semen contain too few sperm

o

TREATMENT:

natural/synthetic androgens such as testosterone

// Viagra (sildenafil) is an enzyme inhibitor causes smooth muscle surrounding erectile tissue
to relax more blood can be pumped into them during erection process

In Vitro Fertilisation (IVF)

1. FSH is injected in woman
2. Just before ovulation eggs are collected and matured
3. Fertilisation collected sperm sample is added to collected mature egg
a. Nucleus of sperm is micro-injected into the egg
b. Fertilisation outside the body in a plastic disc
4. Advantage: possible to screen embryos for genetic defects
5. Maximum of three are transferred into the uterus

The development of the Placenta

The placenta begins to form and grow during the first 4 weeks, due to the tissue of the embryo
invading the wall of the uterus. The placenta is soft and has capillaries filled with the embryos
blood. The wall of the uterus has large spaces filled with the mothers blood. The wall of the
placenta is very thin which brings the mothers blood supply alongside the foetus to allow the
exchange of food and oxygen to the foetus, and for the foetal waste and carbon dioxide to
transfer to the mother. The blood of the mother and foetus do not mix, but substances are
exchanged through the placenta by diffusion. The developing foetus does not breathe within the
uterus, but instead it uses the placenta to get what it needs to develop and survive.

The umbilical cord

Oxygen and food materials in the mothers blood diffuse across the placenta into the embryos
blood and then carried along the umbilical cord to the embryo. Carbon dioxide and waste diffuse
the other way and are carried away in the mothers blood. The umbilical cord connects the baby
to the mothers placenta. The cord contains an artery, which carries waste products from the
developing baby to the placenta, and a vein, which carries the food and oxygen to the foetus
from the mother.
The amnion
A strong membrane called the amnion, which makes a fluid called amniotic fluid, protects the
developing baby. This helps to protect the foetus from being damaged by the mother during her
normal activities over the nine months of development.

Functions of the Amnion

"surrounds embryo like a fluid filled balloon"

suspends embryo in amniotic fluid that: a. protects against mechanical injury/shock and
adhesions, and b. allows for fetal growth and movement

amniotic fluid contains 200 proteins: used for assessing status of mother & fetus

Amniotic fluid contains cells from embryo: used in genetic analysis (e.g., sex, anomalies)

The human embryo develops in the mother's uterus within a

fluid-filled sac
called the amnion. The primary function of the amnion is to
create a roomy, weightless, protective chamber in which the
fetus can grow freely. As the embryo grows, the amnion
expands as well. The amount of fluid contained in the amnion
(known as amniotic fluid) is important for maintaining the
size of the cavity. If there is an inadequate supply of
amniotic fluid will constrain the growth of the fetus.
Resulting in severe malformations. The lungs will not develop
properly If there is insufficient amniotic fluid, the wall of
the mother's uterus will compress the chest of the fetus,
restricting the development of the lungs. Amniotic fluid may
be a source of fetal nutrients If the fetus fails to excrete
urine into the amniotic sac (this occurs when both kidneys
fail to develop and no urine is produced), this results in a
severe shortage of amniotic fluid). In addition to
contributing urine to the amniotic fluid, the fetus also
consumes this fluid by swallowing it. This liquid enters the
fetal intestines where most of it is absorbed into the fetal
blood. Here, it can be processed into urine or, returned to
the maternal blood via the placenta. The fetus actually
produces very little feaces while in the womb. The small
amounts that are produced are excreted into the amnion by the
fetus only late in gestation. A large amount of feaces in the
amniotic fluid is frequently a sign of 'fetal distress'. It
is especially dangerous to infants during delivery because a
large amount of feaces can block the airway and prevent the
infant from breathing in oxygen if it is not removed. In
addition, once the baby is out of the uterus and takes its
first breath, it may inhale small amounts of feaces into its
lungs. This is a particularly serious situation as it can
result in serious illness in the newborn.