2. Fertilization
• Fertilization, the union of male and female
gametes, normally occurs in the ampulla, the
upper third of the oviduct.
• Thus, both the ovum and the sperm must be
to the ampulla.
3. Ovum Transport to the Oviduct
• the ovaries are not in direct contact with the
reproductive tract. The ovum is released into the
abdominal cavity at ovulation. Normally, however,
the oviduct quickly picks up the egg.
• The dilated end of the oviduct cups around the
ovary and contains fimbriae, fingerlike projections
that contract in a sweeping motion to guide the
released ovum into the oviduct. Furthermore, the
fimbriae are lined by cilia that beat in waves toward
the interior of the oviduct— further assuring the
ovum’s passage into the oviduct
• Within the oviduct, the ovum is rapidly propelled by
peristaltic contractions and ciliary action to the
ampulla.
4. Ovum Transport to the Oviduct
• Conception can take place during a limited time span in each cycle (the fertile period).
• If not fertilized, the ovum begins to disintegrate within 12 to 24 hours and is subsequently
phagocytized by cells that line the reproductive tract.
• Fertilization must therefore occur within 24 hours after ovulation, when the ovum is still viable.
• Sperm typically survive about 48 hours but can survive up to 5 days in the female reproductive
tract, so sperm deposited from 5 days before ovulation to 24 hours after ovulation may be able
to fertilize the released ovum, although these times vary considerably.
• Occasionally, an ovum fails to be transported into the oviduct and remains instead in the
abdominal cavity. Rarely, such an ovum gets fertilized, resulting in an ectopic abdominal
pregnancy, in which the fertilized egg implants in the rich vascular supply to the digestive organs
rather than in its usual site in the uterus. An abdominal pregnancy often leads to life-threatening
hemorrhage because the digestive organ blood supply is not primed to respond appropriately to
implantation as the endometrium is. If this unusual pregnancy proceeds to term, probability of
maternal complications at birth is greatly increased because the digestive vasculature is not
designed to “seal itself off ” after birth as the endometrium does.
5. Sperm Transport to the Oviduct
• After sperm are deposited in the vagina, they must travel through the cervical canal, through the uterus, and then up to the egg in the upper
third of the oviduct.
• The first sperm arrive in the oviduct within half an hour after ejaculation. Even though sperm are mobile by means of whiplike contractions of
their tails, 30 minutes is too soon for a sperm’s mobility to transport it to the site of fertilization. To make this journey, sperm need the help of
the female reproductive tract.
• The first difficulty is passage through the cervical canal. Throughout most of the cycle, the cervical mucus is too thick to permit sperm
penetration. The cervical mucus becomes thin and watery enough to permit sperm to penetrate only when estrogen levels are high. The canal
remains penetrable for only 2 or 3 days during each cycle, around the time of ovulation.
• Once sperm have entered the uterus, contractions of the myometrium churn them around. This action quickly disperses sperm throughout the
uterine cavity. When sperm reach the oviduct, they are propelled to the fertilization site by upward contractions of the oviduct smooth muscle.
• These myometrial and oviduct contractions that facilitate sperm transport are induced by the high estrogen level just before ovulation,
aided by seminal prostaglandins.
• There are several chemoattractants released by follicular cells (corona radiata) that further attract sperm for fertilization, including
progesterone, which binds with fast-responding nongenomic surface membrane receptors on the sperm.
• On binding, progesterone opens Ca-permeable cation channels called CatSper channels found exclusively in the plasma membrane of a sperm
tail. The resultant Ca entry is crucial for the following fertilization- related events in sperm: (1) capacitation -enhancement of sperm’s capacity
to fertilize in the male and female reproductive tracts. (2) hyperactivated motility, and (3) the acrosome reaction. Thus CatSper activation is
essential for male fertility.
• When Ca floods into the cell on progesterone-induced opening of CatSper channels, sperm switch from their usual smooth swimming motion
to a highly asymmetric, frantic beating of the tail called hyperactivated motility. This more powerful type of motility generates the extra
thrust needed for sperm to penetrate the corona radiata and zona pellucida to enter the egg.
6. Fertilization
• 165 million sperm typically deposited in a single ejaculate,
only a few thousand make it to the site of fertilization.
• acrosomal enzymes of many sperm are needed to break
down the barriers surrounding the ovum.
• sperm concentration must be so high (20 million/mL of
semen) for a man to be fertile.
• The tail of the sperm is used to maneuver for final
penetration of the ovum.
• To fertilize an ovum, a sperm must first pass through the
corona radiata and zona pellucida surrounding it.
• The sperm penetrates the corona radiata by means of
membrane- bound enzymes in the surface membrane that
surrounds the head
7. Fertilization
• fertilin, a plasma membrane protein on
the sperm head, binds with ZP3, a
glycoprotein in the outer layer of the
zona pellucida
• Binding of the sperm head to ZP3 triggers
the Ca-dependent acrosome reaction.
Calcium that enters the sperm tail
through the opened CatSper channels
rapidly moves within a few seconds to
the head, where it participates in the
acrosome reaction.
• Fertilization- induced release of
intracellular Ca into the ovum cytosol
triggers the exocytosis of these cortical
granules (+seal off tunnels in progress to
keep other penetrating sperm from
advancing)
• released Ca in the ovum cytosol triggers
the 2nd meiotic division of the egg
• Within an hour, the sperm and egg
nuclei fuse, thanks to a centrosome
provided by the sperm that forms
microtubules to bring the male and
female chromosome sets together for
uniting.
• victorious sperm also activates ovum
enzymes essential for the early
embryonic developmental program.
8. Early stages of development from
fertilization to implantation
• During the first 3 to 4 days following
fertilization, the zygote remains within the
ampulla because a constriction between the
ampulla and the remainder of the oviduct
canal prevents further movement of the
zygote toward the uterus.
• During this time, zygote rapidly undergoes a
number of mitotic cell divisions to form a
solid ball of cells called the morula
• Meanwhile, the rising levels of
progesterone from the newly developed CL
after ovulation stimulates release of
glycogen from the endometrium into the
reproductive tract lumen for use as energy
by the early embryo.
• The nutrients stored in the cytoplasm of the
ovum can sustain the embryo for less than a
day.
9. Descent of the Morula to the Uterus
• About 3 to 4 days after ovulation, progesterone is being produced in sufficient quantities to relax
the oviduct constriction, thus permitting the morula to be rapidly propelled into the uterus by
oviductal peristaltic contractions and ciliary activity.
• The temporary delay before the developing embryo passes into the uterus lets enough nutrients
accumulate in the uterine lumen to support the embryo until implantation can take place. If the
morula arrives prematurely, it dies.
• When the morula descends to the uterus, it floats freely within the uterine cavity for another 3
to 4 days, living on endometrial secretions and continuing to divide.
• During the first 6 to 7 days after ovulation, while the developing embryo is in transit in the
oviduct and floating in the uterine lumen, the uterine lining is simultaneously being prepared for
implantation under the influence of luteal-phase progesterone. During this time, the uterus is in
its secretory, or progestational phase, storing up glycogen and becoming richly vascularized.
• Occasionally, the morula fails to descend into the uterus and continues to develop and implant in
the lining of the oviduct. This leads to an ectopic tubal pregnancy, which must be terminated.
10. Implantation of the Blastocyst in the
Prepared Endometrium
• By the time the endometrium is suitable for
implantation (about a week after ovulation), the
morula has descended to the uterus and
continued to proliferate and differentiate into a
blastocyst capable of implantation.
• A blastocyst is a single-layer hollow ball of about
50 cells encircling a fluid-filled cavity, with a
dense mass of cells known as the inner cell
mass grouped together at one side and thin
outermost layer, the trophoblast.
11. Implantation of the Blastocyst
in the Prepared Endometrium
• When the blastocyst is ready to implant, its surface becomes sticky.
• Endometrium too has become more adhesive through increased formation of cell adhesion
molecules (CAMs).
• The blastocyst adheres to the uterine lining on the side of its inner cell mass.
• Implantation begins when, on contact with the endometrium, the trophoblastic cells overlying
the inner cell mass release protein-digesting enzymes, which digest pathways between the
endometrial cells, permitting fingerlike cords of trophoblastic cells to penetrate into the depths
of the endometrium, where they continue to digest uterine cells (step 2 ).
• trophoblast performs the dual functions of accomplishing implantation and making metabolic
fuel and raw materials available for the developing embryo as the advancing trophoblastic
projections break down the nutrient-rich endometrial tissue.
• The plasma membranes of the advancing trophoblastic cells degenerate, forming a
multinucleated syncytium that eventually becomes the fetal portion of the placenta.
• endometrial tissue at the contact site undergoes dramatic changes that enhance its ability to
support the implanting embryo. underlying endometrial cells secrete prostaglandins, which
locally increase vascularization, produce edema, and enhance nutrient storage. The
endometrial tissue so modified at the implantation site is called the decidua. After the
blastocyst burrows into the decidua, a layer of endometrial cells covers over the surface of the
hole, completely burying the blastocyst within the uterine lining (step 3 ).
• The trophoblastic layer continues to digest the surrounding decidual cells, providing energy for
the embryo until the placenta develops.
12. Placenta • The glycogen stores in the endometrium are
sufficient to nourish the embryo only during its first
few weeks. Thereafter, placenta takes over.
• The placenta is derived from both trophoblastic and
decidual tissue. It is an unusual organ because it is
composed of tissues of two organisms: the embryo–
fetus and the mother.
• By day 12, the embryo is completely embedded in
the decidua. By this time, the trophoblastic layer is
two cell layers thick and is called the chorion.
• As the chorion continues to release enzymes and
expand, it forms an extensive network of cavities
within the decidua. As the expanding chorion erodes
decidual capillary walls, maternal blood leaks from
the capillaries and fills these cavities.
• The blood is kept from clotting by an anticoagulant
produced by the chorion.
• Fingerlike projections of chorionic tissue extend into
the pools of maternal blood. Soon the developing
embryo sends out capillaries into these chorionic
projections to form placental villi. Some villi extend
completely across the blood-filled spaces to anchor
the fetal portion of the placenta to the endometrial
tissue, but most simply project into the pool of
maternal blood.
13. Placenta
• Each placental villus contains embryonic (later fetal)
capillaries surrounded by a thin layer of chorionic tissue,
which separates the embryonic–fetal blood from the pools of
maternal blood in the intervillous spaces.
• Maternal and fetal blood do not actually mingle, but the
barrier between them is extremely thin.
• All exchanges between these two bloodstreams take place
across this extremely thin barrier.
• This entire system of interlocking maternal (decidual) and
fetal (chorionic) structures makes up the placenta.
• Even though not fully developed, the placenta is well
established and operational by 5 weeks after implantation. By
this time, the heart of the developing embryo is pumping
blood into the placental villi and to the embryonic tissues.
• Throughout gestation, fetal blood continuously traverses
between the placental villi and the circulatory system of the
fetus by means of two umbilical arteries and one umbilical
vein, which are wrapped within the umbilical cord, a lifeline
between the fetus and the placenta.
• The maternal blood within the placenta is continuously
replaced as fresh blood enters through uterine arterioles;
percolates through the intervillous spaces, where it exchanges
substances with fetal blood in the surrounding villi; and then
exits through uterine venules.
14. Amnion
• Meanwhile, during the time of implantation and early placental development, the inner cell
mass forms a fluid-filled amniotic cavity between the trophoblast–chorion and the portion
of the inner cell mass destined to become the fetus.
• The epithelial layer that encloses the amniotic cavity is called the amniotic sac, or amnion.
• As it continues to develop, the amniotic sac eventually fuses with the chorion, forming a
single combined membrane that surrounds the embryo–fetus.
• The fluid in the amniotic cavity, the amniotic fluid, which is similar in composition to
normal ECF, surrounds and cushions the fetus throughout gestation
15. Functions of the Placenta
• Nutrients and O2 move from the maternal blood across the thin
placental barrier into the fetal blood, whereas CO2 and other
metabolic wastes simultaneously move from the fetal blood into the
maternal blood.
• Thus, the mother’s digestive tract, respira- tory system, and kidneys
serve the fetus’s needs and her own.
• The means by which materials move across the placenta depends on
the substance: some cross by simple diffusion, others through special
transporters or endocytosis
• Placenta also becomes a temporary endocrine organ during
pregnancy
16. Placental Hormones
• The fetally derived portion of the placenta has the remarkable capacity to secrete a number of hormones essential for maintaining
pregnancy.
• Placenta is unique among endocrine tissues in two regards:
1. it is a transient tissue
2. secretion of its hormones is not subject to extrinsic control. Instead, the type and rate of placental hormone secretion depend
primarily on the stage of pregnancy.
17. Human Chorionic Gonadotropin (hCG)
• secreted by the developing chorion
• peptide hormone that prolongs the life span of the corpus luteum (binds to the
same receptor as LH, stimulates and maintains the CL so that it does not
degenerate. LH itself is suppressed through feedback inhibition by the high levels
of progesterone).
• corpus luteum of pregnancy, as a result, grows even larger and produces
increasingly greater amounts of estrogen and progesterone for an additional 10
weeks until the placenta takes over secretion of these steroid hormones
• implanted blastocyst saves itself from being flushed out in menstrual flow by
producing hCG: because of the persistence of estrogen and progesterone, the
thick, pulpy endometrial tissue is maintained instead of sloughing. Accordingly,
menstruation ceases during pregnancy.
• In a male fetus, hCG also stimulates the precursor Leydig cells in the fetal testes
to secrete testosterone, which masculinizes the developing reproductive tract.
18. Human Chorionic Gonadotropin (hCG)
• The secretion rate of hCG increases rapidly during early pregnancy to
save the CL from demise.
• Peak secretion of hCG occurs about 60 days after the end of the last
menstrual period.
• By the 10th week of pregnancy, hCG output declines to a low rate of
secretion that is maintained for the duration of gestation.
• The fall in hCG occurs because the placenta has begun to secrete
substantial quantities of estrogen and progesterone, which inhibit
hCG secretion.
• By this time, the CL of pregnancy is no longer needed for its steroid
hormone output, Therefore the CL of pregnancy is the source of
estrogen and progesterone during the first trimester of gestation, and
the placenta takes over this role during the last two trimesters.
• The CL of pregnancy partially regresses as hCG secretion drops, but it is
not converted into scar tissue until after delivery of the baby.
19. Human Chorionic Gonadotropin (hCG)
• hCG is eliminated from the body in the urine.
• Pregnancy tests can detect hCG in urine as early as the first month
of pregnancy, about 2 weeks after the first missed menstrual
period.
• A frequent early clinical sign of pregnancy is morning sickness - daily
bout of nausea and vomiting that often occurs in the morning but can
take place at any time of day.
• Because this condition usually appears shortly after implantation and
coincides with the time of peak hCG production, this can be caused
by hCG acting on the chemoreceptor trigger zone next to the
vomiting center.
20. Estrogen and Progesterone
• In the case of estrogen, the placenta does not have all the enzymes needed for
complete synthesis of this hormone. Estrogen synthesis requires a complex
interaction between the placenta and the fetus.
• The placenta converts the DHEA produced by the fetal adrenal cortex into
estrogen.
• The placenta cannot produce estrogen until the fetus has developed to the
point that its adrenal cortex is secreting DHEA into the blood.
• The placenta extracts DHEA from the fetal blood and converts it into estrogen,
which it then secretes into the maternal blood.
• The primary estrogen synthesized by the placenta is estriol, in contrast to the
main estrogen product of the ovaries, estradiol.
• In the case of progesterone, the placenta can synthesize it soon after
implantation. Even though the early placenta has the enzymes necessary to
convert cholesterol extracted from the maternal blood into progesterone, it
does not produce much of it because the amount of progesterone produced is
proportional to placental weight.. The notable increase in circulating
progesterone in the last 7 months of gestation reflects placental growth during
this period.
21. Roles of Estrogen and Progesterone During
Pregnancy
ESTROGEN
• Stimulates growth of myometrium (increases size)
🡪 stronger uterine musculature needed to expel
fetus during labour
• Promotes development of ducts within mammary
glands, through which milk is ejected during
lactation
PROGESTERONE
• Suppresses contractions of uterine myoetrium
(prevents miscarriage)
• Promotes formation of a thick mucus plug in
cervical canal 🡪 prevention of vaginal
contaminants reaching uterus
• Stimulates development of milk glands in
breats in preparation of lactation
22. Changes during late gestation preparing for
parturition
• Parturition (labor, delivery, or birth) requires:
(1) dilation of the cervical canal to accommodate passage of the fetus
(2) contractions of the uterine myometrium that are sufficiently strong to expel the fetus.
• Changes take place during late gestation in preparation for the onset of parturition.
• During the first two trimesters of gestation, the uterus remains relatively quiet because
of the inhibitory effect of the high levels of progesterone on the uterine muscle. During
the last trimester, however, the uterus becomes progressively more excitable, so mild
contractions (Braxton–Hicks contractions) are experienced.
• Throughout gestation, the exit of the uterus remains sealed by tightly closed cervix. As
parturition approaches, the cervix begins to soften (or “ripen”) as a result of the
dissociation of its tough connective tissue (collagen) fibers. This is caused largely by
relaxin, a peptide hormone produced by the CL of pregnancy and by the placenta.
• Relaxin also “relaxes” the birth canal by loosening the connective tissue between pelvic
bones.
23. Parturition: Role of Estrogen
1. high levels of estrogen promote synthesis of connexons within the
uterine smooth muscle cells. These myometrial cells are not functionally
linked to any extent throughout most of gestation. The newly manufactured
connexons are inserted in the myometrial plasma membranes to form gap
junctions that electrically link together the uterine smooth muscle cells so
that they become able to contract as a coordinated unit
2. increase the concentration of myometrial receptors for oxytocin 🡪
increased uterine responsiveness to oxytocin
3. increasing estrogen levels promote production of local
prostaglandins that contribute to cervical ripening by stimulating cervical
enzymes that degrade local collagen fibers. These prostaglandins also
increase uterine responsiveness to oxytocin.
24. Parturition: Role of Oxytocin
• Oxytocin is a peptide hormone produced by the hypothalamus,
stored in the posterior pituitary, and released into the blood from the
posterior pituitary on nervous stimulation by the hypothalamus
• oxytocin plays the key role in the progression of labor.
• powerful uterine muscle stimulant
• circulating levels of oxytocin remain constant before the onset of
labor, however, labor begins when myometrial responsiveness to
oxytocin reaches a critical thresh- old that permits onset of strong,
coordinated contractions in response to ordinary levels of circulating
oxytocin.
25. Parturition: Role of CRH
CRH (secreted by the fetal portion of the placenta into both the maternal and the fetal circulations) drives the
manufacture of placental estrogen, ultimately dictating the timing of the onset of labor, promotes changes in the
fetal lungs needed for breathing air
• In the fetus, much of the CRH comes from the placenta rather than solely from the fetal hypo- thalamus. The
additional cortisol secretion summoned by the extra CRH promotes fetal lung maturation.
• bumped-up rate of DHEA secretion by the adrenal cor- tex in response to placental CRH leads to the rising levels
of placental estrogen secretion because the placenta converts DHEA from the fetal adrenal gland into estrogen,
which enters the maternal bloodstream
• When sufficiently high, this estrogen sets in motion the events that initiate labor.
• Thus, pregnancy duration and delivery timing are determined largely by the placenta’s rate of CRH production.
(“placental clock”)
• The ticking of the placental clock is measured by the rate of placental secretion of CRH. As the pregnancy
progresses, CRH levels in maternal plasma rise. data suggest that when a critical level of placental CRH is reached,
parturition is triggered.
• What controls placental secretion of CRH? Yet unkown
26. Parturition: Role of Inflammation
• new evidence suggests that inflammation plays a central role in the labor process.
• Key to this inflammatory response is activation of nuclear factor kB (NF-kB) in the
uterus.
• NF-kB boosts production of inflammatory cytokines such as IL-8 and prostaglandins that
increase the sensitivity of the uterus to contraction-inducing chemical messengers and
help soften the cervix.
• What activates NF-kB?
stretching of the uterine muscle and the presence of a specific pulmonary surfactant
protein SP-A (stimulated by the action of CRH on the fetal lungs) in the amniotic fluid from
the fetus. SP-A promotes migration of fetal macrophages (see p. 393) to the uterus. These
macrophages, in turn, produce the inflammatory cytokine interleukin 1b (IL-1b) that
activates NF-kB. In this way, fetal lung maturation contributes to the onset of labor.
• Bacterial infections and allergic reactions can lead to premature labor by activating NF-
kB. Also, multiple- fetus pregnancies are at risk for premature labor, likely because the
increased uterine stretching triggers earlier activation of NF-kB.
27. Parturition
• Once uterine responsiveness to oxytocin reaches a critical level and regular uterine contractions begin,
myometrial contractions progressively increase in frequency, strength, and duration throughout labor until
they expel the uterine contents.
• At the beginning of labor, contractions lasting 30 seconds or less occur about every 25 to 30 minutes; by the
end, they last 60 to 90 seconds and occur every 2 to 3 minutes.
• As labor progresses, a positive-feedback cycle involving oxytocin and prostaglandin ensues, increasing
myometrial contractions.
• Each uterine contraction begins at the top of the uterus and sweeps downward, forcing the fetus toward
the cervix. Pressure of the fetus against the cervix does two things:
1. fetal head pushing against the softened cervix wedges open the cervical canal.
2. stimulation of receptors in the cervix in response to fetal pressure sends a neural signal up the spinal
cord to the hypothalamus, which in turn triggers oxytocin release from the posterior pituitary 🡪 more
powerful uterine contractions. As a result, the fetus is pushed more forcefully against the cervix,
stimulating the release of even more oxytocin, and so on. This cycle is reinforced as oxytocin stimulates
prostaglandin production by the decidua. As a powerful myometrial stimulant, prostaglandin further
enhances uterine contractions.
Oxytocin secretion, prostaglandin production, and uterine contractions continue to increase in positive-
feedback fashion throughout labor until delivery relieves the pressure on the cervix.
29. Stages of Labor
• At the onset of labor or sometime during the first stage, the amniotic sac ruptures. As amniotic
fluid escapes out of the vagina, it helps lubricate the birth canal.
Stage 1: Cervical Dilation
• Longest stage, (several hours to as long as 24
hours in a first pregnancy)
• cervix forced to dilate to accommodate the
diameter of the baby’s head, (usually to a
max of 10 cm)
• head - largest diameter of the baby’s body. If
the baby approaches the birth canal feet first,
the feet may not dilate the cervix enough to
let the head pass
Stage 2: Delivery of Baby
• stretch receptors in the vagina activate a
neural reflex that triggers contractions of the
abdominal wall in synchrony with the uterine
contractions 🡪 greatly increasing force
pushing the baby through the birth canal.
• Can be done voluntarily too - in unison with
each uterine contraction ( “pushing” with each
“labor pain”).
• lasting 30 to 90 minutes.
Stage 3: Delivery of Placenta
• Shortly after delivery of the baby, a second
series of uterine contractions separates the
placenta from the myometrium and expels it
through the vagina.
• shortest stage, being completed within 15 to 30
minutes after the baby is born.
• After the placenta is expelled, continued
contractions of the myometrium constrict the
uterine blood vessels supplying the site of
placental attachment to prevent hemorrhage.
30. Uterine Involution
• After delivery, the uterus shrinks to its pregestational size, a process known as
involution, which takes 4 to 6 weeks to complete.
• During involution, the remaining endometrial tissue not expelled with the
placenta gradually disintegrates and sloughs off, producing a vaginal discharge
called lochia that continues for 3 to 6 weeks following parturition. After this
period, the endometrium is restored to its nonpregnant state.
• Involution occurs largely because of the precipitous fall in circulating estrogen
and progesterone when the placental source of these steroids is lost at delivery.
• The process is facilitated in mothers who breast-feed their infants because
oxytocin is released in response to suckling. this periodic nursing-induced release
of oxytocin promotes myometrial contractions that help maintain uterine muscle
tone, enhancing involution.
• Involution is usually complete in about 4 weeks in nursing mothers but takes
about 6 weeks in those who do not breast-feed.
