OOGENESIS

• Oogenesis (ovogenesis) is the sequence of events by which oogonia are

transformed into mature oocytes
• This maturation process begins before birth and is completed after
puberty
• Oogenesis continues to menopause, which is permanent cessation of the
menses (bleeding associated with the menstrual cycles)
 2 maturation processes of oocytes are involved;
 Prenatal maturation
 Postnatal maturation
Prenatal Maturation of Oocytes
• Primordial germ cells (46, 2N) migrate from the wall of the yolk sac and
arrive in the ovary at 5th week and differentiate into oogonia (46, 2N),
which populate the ovary through mitotic division.
• A majority of oogonia undergo mitotic division to form primary oocytes
(46, 2N)
• by the 5th month of prenatal development, the total number of germ cells in
the ovary reaches its maximum, which is estimated at 7 million
 Note: All primary oocytes are formed by the 5th month of fetal life
• At this time, cell death begins, and many oogonia as well as
primary oocytes become atretic
• By the 7th month, the majority of oogonia have degenerated
except for a few near the surface
 Note: No oogonia are present at birth
• All surviving primary oocytes have entered prophase of meiosis I,
and most of them are individually surrounded by a single layer of
flattened, follicular epithelial cells
• The primary oocytes enclosed by this layer of cells constitutes a
primordial follicle
• Primary oocytes begin the first meiotic division before birth, but
completion of prophase 1 does not occur until puberty
• The follicular cells surrounding the primary oocyte are believed to
secrete a substance, oocyte maturation inhibitor (OMI) which
keeps the meiotic process of the oocyte arrested
 Postnatal Maturation of Oocytes
• Beginning during puberty, usually one follicle matures each
month and ovulation occurs, except when oral contraceptives are
used
• The total number of primary oocytes at birth is estimated to vary
from 600,000 to 800,000
• only approximately 40,000 are present by the beginning of
puberty, and fewer than 500 will be ovulated
• As the primary oocyte enlarges during puberty, the follicular
epithelial cells become cuboidal in shape and then columnar,
forming a primary follicle
• The primary oocyte soon becomes surrounded by a covering of
amorphous acellular glycoprotein material, the zona pellucida
Note: No primary oocytes form after birth in females, in contrast to
the continuous production of primary spermatocytes in males
• The primary oocytes remain dormant in the ovarian follicles until
puberty
• As a follicle matures, the primary oocyte increases in size and,
shortly before ovulation, the 1ST meiotic division is completed
giving rise to a secondary oocyte and the first polar body
• Unlike the corresponding stage of spermatogenesis, there is
formation 2 daughters of unequal size, this is because the division
of cytoplasm is unequal, each with 23 double structured
chromosomes
• The secondary oocyte receives almost all the cytoplasm and the
first polar body receives very little
• The 1st polar body is a small, nonfunctional cell that soon
degenerates
 Note: The first polar may also undergo a second meiotic division
• The first polar body lies between the zona pellucida and the cell
membrane of the secondary oocyte in the perivitelline space
• The cell then enters meiosis II, but it is arrested at metaphase II
approximately 3 hours before ovulation
 Note: If a sperm penetrates the secondary oocyte, the second
meiotic division is completed, and most cytoplasm is again
retained by one cell, the fertilized oocyte (zygote), while the 2nd
polar body receive little cytoplasm
• If not fertilized, the cell degenerates approximately 24 hours after
ovulation
• The other cell, the 2nd polar body, also a small nonfunctional cell,
soon degenerates
• As soon as the polar body is extruded, maturation of the oocyte is
complete
• Of these, only about 400-500 become secondary oocytes and
are expelled at ovulation during the reproductive period
• Few of these oocytes, if any, are fertilized and become mature
• The number of oocytes that ovulate is greatly reduced in
women who take oral contraceptives because the hormones in
them prevent ovulation from occurring
 Ovaries
Intro:
• The ovaries are almond-shaped reproductive glands located close to
the lateral pelvic walls on each side of the uterus
functions
 They produce oocytes
 They also produce estrogen and progesterone
 Estrogen and progesterone are hormones responsible for the;
 development of secondary sex characteristics
 regulation of pregnancy
Female reproductive cycles
• females undergo reproductive cycles (sexual cycles), involving
activities of the hypothalamus of the brain, pituitary gland
(hypophysis), ovaries, uterus, uterine tubes, vagina, and mammary
glands and this commences at puberty
• These monthly cycles prepare the reproductive system for pregnancy
• Gonadotropin-releasing hormone is synthesized by neurosecretory
cells in the hypothalamus and is carried by the hypophysial portal
system to the anterior lobe of the pituitary gland
• Gonadotropin-releasing hormone stimulates the release of 2
hormones namely:
 Follicle-stimulating hormone (FSH)
 Luteinizing hormone (LH)
• These 2 hormones act on the ovaries:
 Follicle-stimulating hormone (FSH) stimulates the;
 development of ovarian follicles
 production of estrogen by the follicular cells
 Luteinizing hormone (LH)
 Final stages of maturation of ovarian follicles
 serves as the "trigger" for ovulation (release of secondary oocyte)
 stimulates the follicular cells and corpus luteum to produce
progesterone
 Ovarian cycle
• These are cyclic changes in the ovaries, and these changes are
produced by FSH and LH
• These changes include:
I. development of follicles
II. ovulation
III. Formation of the corpus luteum

 Development of follicles
• Development of an ovarian follicle is characterized by:
I. Growth and differentiation of primary oocyte
II. Proliferation of follicular cells
III. Formation of zona pellucida
IV. Development of the theca folliculi
1. Proliferation of follicular cells
• As primordial follicles begin to grow, surrounding follicular cells
change from flat to cuboidal in shape and then columnar, forming
a primary follicle
2. Formation of zona pellucida
• the follicular (granulosa) cells and the oocyte secrete a layer of
glycoproteins on the surface of the oocyte, forming the zona
pellucida
3. Development of theca folliculi
• As the primary follicle continues to grow, the adjacent
(surounding) connective tissue organizes into a capsule, called the
theca folliculi
Continuous growth causes cells of the theca folliculi then
differentiate into:
 an inner layer of secretory cells, called the theca interna
 and an outer fibrous capsule, called the theca externa
Theca externa

Theca interna

antrum

Primary ooctye

Secondary/ Vesicular follicle

Matured vesicular follicle
• As development continues, fluid-filled spaces appear between
follicular (granulosa) cells
• The fluid filled space is crescent-shaped, but with time, it enlarges
which coalesce to form a single large cavity, the antrum, which
contains follicular fluid
• When a large cavity called antrum forms, the ovarian follicle is
refered to as a vesicular or secondary follicle
• The primary oocyte is pushed to one side of the follicle, where it is
surrounded by a mound of follicular cells, the cumulus oophorus,
that projects into the antrum
• The secondary/ vesicular follicular continues to grow and become
matured having a diameter of about 25mm or more
• At maturity, it is called the mature vesicular/ mature secondary or
Graafian follicle
 Note
 The early development of ovarian follicles is induced by FSH, but
final stages of maturation require LH as well
 Growing follicles produce estrogen, hormone that regulates
development and function of the reproductive organs

Ovulation
 This is the release of a secondary oocyte from the ovarian follicle
• In a few days before ovulation, under the influence of FSH and LH,
the secondary follicle grows rapidly to a diameter of about 25 mm to
become mature vesicular/ mature secondary or Graafian follicle
 Coincident with final development of the vesicular follicle, there is an
abrupt increase in LH that causes;
1. the primary oocyte to complete meiosis I
2. the follicle to enter the preovulatory mature vesicular stage
 Meiosis II is also initiated, but the secondary oocyte is arrested in
metaphase approximately 3 hours before ovulation
 In the meantime, the surface of the ovary begins to bulge locally, and
at the apex, an avascular spot, the stigma, appears
 For the oocyte to be released, 2 events occur which are caused by LH
surge:
I. it increases collagenase activity, resulting in digestion of collagen fibers
(connective tissue) surrounding the follicle
II. Prostaglandin levels also increase in response to the LH surge and cause
local muscular contractions in the ovarian wall
• Those contractions extrude the oocyte, which together with its surrounding
follicular (granulosa) cells from the region of the cumulus oophorus,
• this causes ovulation in which oocyte floats out of the ovary
• Some of the cumulus oophorus cells then rearrange themselves around the
zona pellucida to form the corona radiata

 Note:
 Ovulation is triggered by a surge of LH production
 Ovulation usually follows the LH peak by 12 to 24 hours
 The LH surge, elicited by the high estrogen level in the blood, appears to
cause the stigma to balloon out, forming a vesicle
 Clinical correlates
 During ovulation, some women feel a variable amount of abdominal pain
called mittelschmerz also known as middle pain because it normally
occurs near the middle of the menstrual cycle
 In these cases, ovulation results in slight bleeding into the peritoneal
cavity, which results in sudden constant pain in the lower abdomen.
 Mittelschmerz may be used as a symptom of ovulation
 Other signs of ovulation include
1. Changes in the cervical mucus:
• When you're not ovulating, cervical mucus may appear sticky, creamy, or
may be entirely absent
• As ovulation approaches, cervical mucus becomes more abundant, takes
on a watery to raw-egg-white-like consistency(slippery egg white looking
discharge), and stretches up to an inch or more between your fingers
2. increase libido/ increase urge for sex
3. Tenderness of the breast
4. Swollen vagina or vulva
 but there are better symptoms, such as the slight drop in basal
body temperature
• For most women, prior to ovulation, the basal body temperature is
rather consistent
• As one get closer to ovulation, one may have a slight decline, but it
will be followed by a sharp increase after ovulation.
• The increase in temperature is the sign that ovulation has just
occurred
 Also the use of ovulation predictor kits (OPKs)help to detect the
LH surge, which occurs 12 to 36 hours before ovulation, you can
be sure to have sex at just the right time for conception

 Some women fail to ovulate, this is called anovulation, because of

a low concentration of gonadotropins
• In these cases, administration of an agent to stimulate
gonadotropin release and hence ovulation can be employed
• Although such drugs are effective, they often produce multiple
ovulations, so that the risk of multiple pregnancies is 10 times
higher in these women than in the general population
 antrum Theca
Luteal cells
interna

Blood
vessels

Theca externa

A : PREOVULATORY FOLLICLE
B: OVULATION C: CORPUS LUTEUM

fibrin
Corpus Luteum
• Shortly after ovulation, the walls of the ovarian follicle and theca
folliculi collapse and are thrown into folds
• Under LH influence, they develop into a glandular structure, called
corpus luteum
• Corpus luteum secretes;
1. Mainly progesterone and
2. some estrogen
• progesterone and estrogen, cause the endometrial glands to secrete
and prepare the endometrium for implantation of the blastocyst
• If the oocyte is fertilized, the corpus luteum enlarges to form a
corpus luteum of pregnancy and increases its hormone production.
• Degeneration of the corpus luteum is prevented by human chorionic
gonadotropin
• The corpus luteum of pregnancy remains functionally active
throughout the first 20 weeks of pregnancy
• If the oocyte is not fertilized, the corpus luteum involutes and
degenerates 10 to 12 days after ovulation
• It is then called a corpus luteum of menstruation
• The corpus luteum is subsequently transformed into white scar
tissue in the ovary, a corpus albicans
• Except during pregnancy, ovarian cycles normally persist
throughout the reproductive life of women and terminate at
menopause, the permanent cessation of menstruation, usually
between the ages of 48 and 55
 Uterus ( womb)
introduction
• is a thick-walled, pear-shaped muscular organ
dimension
 Length = approx 7-8 cm
 width = approx 5-7cm at its superior part
 thickness= approx 2-3 cm
parts
• consists of 2 major parts
 Body, the expanded superior 2/3
 Cervix, the cylindrical inferior 1/3
The body of the uterus
• narrows from the fundus (the rounded, superior part of the body) to
the isthmus
 Note: the isthmus is the 1cm long constricted region between the
body and cervix
The cervix of the uterus
• is its tapered vaginal end that is nearly cylindrical in shape
• It has a lumen called the cervical canal
• the cervical canal, has constricted openings at each end
• At the upper constricted end is the internal os, while at the
lower constricted end is the external os
• The internal os communicates with the cavity of the uterine
body, while the external os communicates with the vagina
The walls of the body of the uterus
• consist of three layers
 Perimetrium, the thin external layer
 Myometrium, the thick smooth muscle layer
 Endometrium, the thin internal layer
• The perimetrium is firmly attached to the myometrium
The layers of the endometrium
• It has 3 layers
 A thin superficial layer called the compact layer
 A thick middle layer called the spongy layer
 A thin deep layer called the basal layer
• . The basal layer of the endometrium has its own blood supply and
is not sloughed off during menstruation
• The compact and spongy layers collectively are called the
functional layer
• This functional layer disintegrate and are shed during
menstruation and after parturition (delivery of a baby)
Uterine tubes
Intro:
The uterine tubes extend laterally from the horns of the uterus
Dimension
approximately 10 cm long and 1 cm in diameter
Parts
the uterine tube is divided into four parts:
 infundibulum
 ampulla
 isthmus
 uterine part
functions
 carries oocytes from the ovaries and sperms entering from the uterus
to reach the fertilization site in the ampulla of the uterine tube
 conveys the cleaving zygote to the uterine cavity
 Menstrual cycle
• Also called the endometrial cycle
• It constitutes the monthly changes in the internal layer of the
uterus
• During this period, menstruation (flow of blood from the uterus)
is an obvious event
• The average menstrual cycle is 28 days
• day 1 of this (28 days) cycle designated as the day on which
menstrual flow begins
• Menstrual cycles normally vary in length by several days
• In 90% of women, the length of the cycles ranges between 23 and
35 days
• Almost all these variations result from alterations in the duration
of the proliferative phase of the menstrual cycle
Phases of the Menstrual Cycle
• Menstrual phase
• Proliferative phase
• Luteal phase
 Ischemic phase (only occur if the oocyte is not ferterlized)
 Menstrual Phase
• Usually lasts 4 to 5 days
• The functional layer of the uterine wall is sloughed off and discarded
with the menstrual flow-menses (monthly bleeding)
• The blood discharged through the vagina is combined with small
pieces of endometrial tissue
• After menstruation, the eroded endometrium is thin

 Proliferative Phase
• Also known as the follicular /estrogenic phase
• lasting approximately 9 days
• coincides with growth of ovarian follicles and is controlled by
estrogen secreted by these follicles
• There is a 2-3 fold increase in the thickness of the endometrium and
in its water content
• Early during this phase, the surface epithelium reforms and covers the
endometrium
• uterine glands increase in number and length
• the spiral arteries elongate

Luteal Phase
• also called the secretory/ progesterone phase
• lasting approximately 13 days
• coincides with the formation, functioning, and growth of the corpus
luteum
• The progesterone produced by the corpus luteum stimulates the
glandular epithelium to secrete a glycogen-rich material which will
nourish the conceptus before the formation of the placenta
• The uterine glands become wide, tortuous, and saccular, and the
endometrium thickens because of;
 the influence of progesterone and estrogen from the corpus luteum
 and because of increased fluid in the connective tissue
• As the spiral arteries grow into the superficial compact layer, they become
increasingly coiled
• The venous network becomes complex and large lacunae (venous spaces) develop
• Direct arteriovenous anastomoses are prominent features of this stage

If fertilization does not occur:

• The corpus luteum degenerates
• Estrogen and progesterone levels fall and the secretory endometrium enters an
ischemic phase
• Menstruation occurs

 Ischemic Phase
• occurs when the oocyte is not fertilized
• Ischemia (reduced blood supply) occurs as a result of constriction of spiral
arteries giving the endometrium a pale appearance
• There is decrease secretion of hormones, primarily progesterone, by the
degenerating corpus luteum
• a loss of interstitial fluid
• shrinking of the endometrium
• This results in venous stasis and patchy ischemic necrosis (death)
in the superficial tissues
• Eventually, rupture of damaged vessel walls follows and blood
seeps into the surrounding connective tissue
• Small pools of blood form and break through the endometrial
surface, resulting in bleeding into the uterine lumen and from the
vagina
 TRANSPORTATION OF GAMETES
Oocyte Transport:
• During ovulation, the secondary oocyte with the escaping
follicular fluid are expelled from the ovarian follicle
• (the fimbriated end of the uterine tube becomes closely applied to
the ovary
• The fingerlike processes of the tube, fimbriae, move back and
forth over the ovary
• As a result of:
I. sweeping action of the fimbriae
II. fluid currents produced by the cilia of the mucosal cells of the
fimbriae ; the secondary oocyte migrates into the funnel-shaped
infundibulum of the uterine tube
• From the infundibulum, the secondary oocyte passes into the
ampulla of the tube, mainly as the result of peristalsis-movements
(alternate contraction and relaxation) of the wall of the tube
Sperm transport
• Sperms are produced in the testes and they are temporarily stored
in the epididymis
• from their storage site in the epididymis, (mainly in the tail of the
epididymis), the sperms are rapidly transported to the urethra by
the ductus (Vas) deferens
• by peristaltic contractions of the thick muscular coat of the ductus
deferens
• (The accessory sex glands- seminal glands (vesicles), prostate,
and bulbourethral glands-produce secretions that are added to the
sperm-containing fluid in the ductus deferens and urethra
• From 200 to 600 million sperms are deposited around the external
os of the uterus and in the fornix of the vagina during sexual
intercourse
• The sperms pass slowly through the cervical canal by movements
of their tails
• As semen moves in the cervical canal, an enzyme which is
produced by the seminal glands called vesiculase coagulates
(hardens) some of the semen or ejaculate and forms a vaginal
plug (barrier) that may prevent the backflow of semen into the
vagina
• Prostaglandins in the semen helps to stimulate uterine motility at
the time of intercourse and assist in the movement of sperms to the
site of fertilization in the ampulla of the tube
• Fructose is secreted by the seminal glands, is an energy source
for the sperms in the semen
note
• When ovulation occurs, the cervical mucus increases in amount
and becomes less viscid, making it more favorable for sperm
transport
• Passage of sperms through the uterus and uterine tubes results
mainly from muscular contractions of the walls of these organs
• The volume of sperm or ejaculate (sperms suspended in secretions
from accessory sex glands) averages 3.5 mL, with a range of 2 to 6
mL
• The sperms move 2 to 3 mm per minute, but the speed varies with the
pH of the environment
• They are nonmotile during storage in the epididymis, but become
motile in the ejaculate
• They move slowly in the acid environment of the vagina,
• but move more rapidly in the alkaline environment of the uterus
 Note:
It is not known how long it takes sperms to reach the fertilization site,
but the time of transport is probably short
• Motile sperms have been recovered from the ampulla (site of
fertilization) of the uterine tube 5 minutes after their deposition near
the external uterine os
• Some sperms, however, take as long as 45 minutes to complete the
journey
• Only approximately 300-500 sperms reach the fertilization site
• Most sperms degenerate and are resorbed by the female genital
tract
Maturation of sperms
• Freshly ejaculated sperms cannot fertilize oocytes
• In order for the sperms to fertilize the oocytes, they must undergo
I. a period of conditioning called capacitation
II. Acrosomal reaction
Capacitation
• Capacitation lasts for about 7 hours
For capacitation of sperms to occur,
• a glycoprotein coat and seminal plasma proteins are removed from
the plasma membrane that overlies the acrosomal region of the
spermatozoa
• Only capacitated sperms can pass through the corona cells (corona
radiata) and undergo the acrosome reaction

Acrosome reaction
Note:
• The zona is a glycoprotein shell surrounding the egg that facilitates
and maintains sperm binding and induces the acrosome reaction
• The intact acrosome of the sperm binds with a zona glycoprotein
(ZP3/ zona protein 3) on the zona pellucida
• Release of acrosomal enzymes (acrosin) allows sperm to penetrate
the zona pellucida, thereby coming in contact with the plasma
membrane of the oocyte
• As soon as the head of a sperm comes in contact with the oocyte
surface, the permeability of the zona pellucida changes
• When a sperm comes in contact with the oocyte surface, lysosomal
enzymes are released from cortical granules lining the plasma
membrane of the oocyte
• In turn, these enzymes alter properties of the zona pellucida to :
 prevent sperm penetration and
 inactivate binding sites for spermatozoa on the zona pellicida
surface
• only one sperm seems to be able to penetrate the oocyte

Studies have shown that the sperm plasma membrane, calcium ions,
prostaglandins, and progesterone play a critical role in the
acrosome reaction
67
 Clinical correlates
Sperm counts
• Sperms account for less than 10% of the semen
• The remainder of the ejaculate consists of the secretions of the
seminal glands, prostate, and bulbourethral glands
• There are usually more than 100 million sperms per milliliter of
semen in the ejaculate of normal males
• men whose semen contains 20 million sperms per milliliter, or 50
million in the total specimen, are probably fertile
• A man with fewer than 10 million sperms per milliliter of semen is
likely to be sterile, especially when the specimen contains
immotile and abnormal sperms
• For potential fertility, 50% of sperms should be motile after 2
hours and some should be motile after 24 hours
• Male infertility may result from a low sperm count, poor sperm motility,
medications and drugs, endocrine disorders, exposure to environmental
pollutants, cigarette smoking, abnormal sperms, taking too much
alcohol, or obstruction of a genital duct such as in the ductus deferens
and represents approximately 30% to 50% of infertility in couples
Vasectomy:
• The most effective method of permanent contraception in the male is
vasectomy, or excision of a segment of each ductus (vas) deferens
• This surgical procedure is reversible in more than 50% of cases
• Following vasectomy, there are no sperms in the semen or ejaculate,
but the volume is the same
Dispermy
• several sperms begin to penetrate the corona radiata and zona
pellucida, usually only one sperm penetrates the oocyte and fertilizes it
• Two sperms may participate in fertilization during an abnormal process
known as dispermy, resulting in a zygote with an extra set of
chromosomes
 Embryological terminologies
Abortion
 This is the premature stoppage of development and expulsion of
a conceptus from the uterus or expulsion of an embryo or fetus
before it is viable-capable of living outside the uterus
 The products of an abortion is called an abortus (i.e. the
embryo/fetus and its membranes)
There are different types of abortion:
 A spontaneous abortion is one that occurs naturally and is most
common during the 3rd week after fertilization
• Approximately 15% of recognized pregnancies end in
spontaneous abortion, usually during the first 12 weeks
 A habitual abortion is the spontaneous expulsion of a dead or
nonviable embryo or fetus in three or more consecutive
pregnancies
 An induced abortion is a birth that is medically induced before 20
weeks (i.e., before the fetus is viable)
• This type of abortion refers to the expulsion of an embryo or fetus
induced intentionally by drugs or mechanical means
 A complete abortion is one in which all the products of conception are
expelled from the uterus
 incomplete abortion  is one with retention of parts of the products of
conception
 A missed abortion is the retention of a conceptus in the uterus after
death of the embryo or fetus
 A miscarriage is the spontaneous abortion of a fetus and its
membranes before the middle of the second trimester (approximately
135 days)
 Threatened abortion
• is a condition that suggests a miscarriage might take place before
the 20th week of pregnancy
• In this case, pregnant women have some vaginal bleeding with or
without abdominal cramps during the first three months of
pregnancy
• When the symptoms indicate a miscarriage is possible, the
condition is called a "threatened abortion."
• (This refers to a naturally occurring event, not medical abortions or
surgical abortions
 Trimester: A period of three calendar months during a pregnancy.
• Obstetricians commonly divide the 9-month period of gestation into
three trimesters
• The most critical stages of development occur during the first
trimester (13 weeks) when embryonic and early fetal development is
occurring