The topic is about reproductive physiology

1. Physiology of Pregnancy
Labour & Lactation

2. Outline
• Fertilization
• Implantation
• Development of placenta
• Hormonal Changes during Pregnancy
• Maternal Responses to Pregnancy
• Parturition
• Lactation
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3. Objectives
At the end of this session the students will able to:
• Discuss the sequential events the gametes under go
during fertilization.
• Describe the hormonal changes that accompany
pregnancy and parturition.
• Summarize maternal response to pregnancy.
• Describe the processes involved in lactation.
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4. Fertilization
• Fertilization is the union of ovum & sperm pronucli
• Fertilization usually occurs in the ampulla of the
uterine tube.
• Fertilization can occur at any time up to about 24-72
hours after ovulation.
It involves:
1. Capacitation of sperm cells
• Involves change in membrane properties, enzyme
activity & motility.
• Occur in female reproductive tract
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5. Fertilization…
Loss of plasma membrane cholesterol (efflux of
cholesterol in to ECF)
Intracellular Ca++ levels increase (through
activation of cAMP & IP3 )
Sperm cell surface antigens are lost
2. Chemo-attraction of the sperm to the ovum by
substances produced by the ovum.
• Soluble molecules released by egg
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6. Fertilization…
3. Penetration of corona radiata, the granulosa cells that
surround the secondary oocyte.
• Sperm’s head bind to the zona pellucida on the
species-specific binding glycoprotein (known as ZP3).
• This activates acrosome reaction  release of
hyaluronidase and proteases penetration of the zona
pellucida & detach of sperm receptor from ZP3.
• Sperm head fuses to the cell membrane of the ovum
and the release of the sperm pronucleus into the
cytoplasm of the ovum.
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7. Fertilization…
• Within a few seconds, the cell membrane of the oocyte
depolarizes, which acts as a fast block to polyspermy.
• Fusion of cell membrane of sperm with the ovum stimulate
phospholipase C which stimulate IP3 → ↑intracellular Ca2+.
• ↑Intracellular Ca2+ drive exocytosis of cortical
granules.
• Cortical granules contain enzymes & hyaline that change
the characteristics of zona pelucida (ZP3) → slow block.
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9. Fertilization…
• Once a sperm nucleus enters a secondary oocyte, the
20 oocyte complete meiosis II formation of female
pronucleus.
• The male pronucleus use microtubules to migrate to
the center of the cell.
• Then it fuses with the female pronucleus to
reconstitute a diploid nucleus  zygote.
• After fertilization, rapid mitotic cell divisions of the
zygote take place.
• The first division of the zygote begins about 24 hours
after fertilization.
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10. Fertilization…
Dizygotic (fraternal) twins
oFertilization of two secondary oocytes by different
sperm
oGenetically not similar
oMay or may not be the same sex
Monozygotic (identical) twins
oContain exactly the same genetic material and the same
sex
oMost of the time develop from separation of cells into
two embryos before implantation.
oIf separations occur after implantation, likely to
produce conjoined twins.
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11. Fertilization…
• By the end of the third day, there are 16 cells known
as morula Blastocyst formation (4-5d) with in zona
pellucida.
• As the fluid increase in the blastocyst it separate in to
two cell layers:
Outer cell layer –trophoblast
• Trophoblast release proteolytic enzymes that digest zona
pellucida
• Forms primitive organ for nourishment
• Gives rise to the placenta and membranes
Inner cell mass –embryoblast
• Grow in to actual embryo (develops into the fetus)
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12. Implantation
• On approximately day 5 or 6 after fertilization, the
blastocyst enters the uterus & zona pellucida breaks.
• About 6-7 days after fertilization, attachment &
implantation into endometrial lining of the uterus start.
• The implantation site is usually on the dorsal wall of
the uterus body.
• The outer layer of cells of blastocyst, the trophoblast
adhere to endometrial lining and grow deep in to the
endometrium by differentiating into:
• Syncytiotrophoblast
• Cytotrophoblast
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13. Implantation...
• Syncytiotrophoblast initially has three general functions:
1. Adhesive – syncytotrophoblast secret adhesive surface
protein for attachment to endometrial surface.
• Secret cadherins, integrins, mucins…
2. Invasive-syncytotrophoblast migrate deep into
endometrium by release (metalloproteinase)
hydrolytic enzymes that digest extracellular matrix.
• Embryo completely burrow itself into superficial
part of endometrium.
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14. Implantation...
• The highly invasive action of syncytiotrophoblast is
inhibited by decidual inhibitors.
• These two layers of trophoblast will surround the embryo
and provide nutrient until the placenta develop.
3. Endocrine function- syncytotrophoblast secret several
important hormones.

15. Implantation...
Human Chorionic Gonadotropin (hCG) –hCG has LH like
effect & maintains development of corpus luteum.
Human Chorionic Somatomammotropin
Progesterone
• The trophoblast cells secrete several angiogenic
factors, including:
• Vascular endothelial growth factor,
• Platelet-derived growth factor (PDGF), and
• Fibroblast growth factor (bFGF), which stimulate
blood vessel development within the villi.
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16. Implantation...
• At the site of implantation, the endometrial cells
undergo decidualization.
• Control extent of trophoblast invasion and influence
trophoblast function.
• This process also converts the high-resistance, low-
capacity uterine vessels into low-resistance, high-
capacitance vessels, essential for growth of the
placenta and fetus.
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17. Development of placenta
• The placenta fully develop at twelve's wks gestation.
• Placenta is the combination of fetal and maternal tissues
that serves as the organ of exchange between mother and
fetus.
 The fetal portion formed by the chorionic villi of the
chorion and
 The maternal portion formed by the decidua basalis of the
endometrium.
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18. Development of placenta…
Functions of the Placenta
1. Transfer of nutrients
• Like other capillary membrane nutrients are transported by
both passive and active transport from the maternal sinus.
2. Exchange of gases
• The fetal blood leaving the placenta has a PO2 of only 30 mm
Hg.

19. Development of placenta…
• This low PO2 is capable of allowing the fetal blood to
transport sufficient O2 to the fetal tissues due to:
• Fetal hemoglobin can carry more oxygen.
• High hemoglobin concentration of fetal blood.
• Bohr effect (diffusion of CO2 in to maternal blood enhance
fetal blood to carry more O2).
3. Excretion of waste products
• Waste products cross the placental membrane by
facilitated or simple diffusion to maternal blood.
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20. Development of placenta
• Because there are higher concentrations of the excretory
products in the fetal blood than in the maternal blood.
4. Formation of barrier b/n mother & fetus blood
• The placenta is impermeable to most large peptide
hormones.
• Peptide hormones larger than 0.7 to 1.2 kd have little
or no access to the fetal compartment.
• But immunoglobulin G, which is actively transported
from mother to fetus during the latter half of gestation.
• Steroid, thyroid hormones and catecholamines cross
the placenta by simple diffusion.
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21. Development of placenta
5. Hormone secretion (endocrine function)
• Placenta secrete diverse number of hormones:
• hCG, hCS, progesterone, and estrogens
• Less amount of proopiomelanocortin (POMC),
• CRH, inhibin, relaxin.
• Steroidogenesis function of placenta can be:
• Dependent on precursors (androgens & pregnenolone) of both
maternal and fetal origin or
• Directly from cholesterol of circulating maternal LDL
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23. Hormonal Changes during Pregnancy
• Corpus luteum during pregnancy secretes estrogens,
progesterone, and relaxin.
• Corpus luteum involutes slowly after the 13th to 17th
week of gestation.
Human Chorionic Gonadotropin (hCG)
• First produced by the syncytiotrophoblast later by
placenta
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24. Hormonal Changes...
• The physiologic factors that regulate hCG secretion
are unknown.
• Detected in the blood as early as 6 d (in the urine as
early as 10-14d) after conception, reach its peak at 8-
10 wks.
•

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26. Hormonal Changes...
Function
• Prevent involution of the corpus luteum at the end of
the monthly female sexual cycle after fertilization.
• Human chorionic gonadotropin also exerts an
interstitial cell–stimulating effect on the testes of the
male fetus.
• Has paracrine role in regulating syncytiotrophoblast
mass and production of trophoblast hormones.
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27. Hormonal Changes...
Human Chorionic Somatomammotropin
• The amount of hCS secretion is proportional to the
size of the placenta.
• Low hCS levels are a sign of placental insufficiency
• Is lactogenic and has a small amount of growth-
stimulating activity.
• Promote development of the breasts
• Increase blood glucose level in the mother (this makes
glucose available for fetus)
• Promotes the release of free fatty acids from the fat
stores of the mother.
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28. Hormonal Changes...
Estrogens
• During pregnancy, the high quantities of estrogens cause:
1. Enlargement of the mother’s uterus
2. Enlargement of the mother’s breasts and growth of the
breast ductal structure, and
3. Enlargement of the mother’s external genitalia.
Relaxin
• Relax the pelvic ligaments of the mother, so that the
symphysis pubis becomes elastic.
• The relaxin helps maintain pregnancy by inhibiting
myometrial contractions.
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29. Hormonal Changes...
Progesterone
• Effects of progesterone that are essential for the normal
progression of pregnancy are:
I. Initiate decidual cells proliferation in the uterine
endometrium.
II. Decreases the contractility of the pregnant uterus, thus
preventing uterine contractions from causing
spontaneous abortion.
III. Stimulate secretory development of endometrium.
• Stromal cells increases; lipid and glycogen deposits
• Increases blood supply to the endometrium
IV. Prepare the mother’s breasts for lactation.
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30. Hormonal Changes...
Maternal Endocrine Alterations
• Endocrine glands of the mother also react markedly to
pregnancy.
• This results mainly from the increased metabolic load
on the mother.
Pituitary Secretion
• APG of the mother enlarges at least 50 % during
pregnancy and increases its production of :
• Corticotropin,
• Thyrotropin  TSH slight enlargement of
the gland
• Prolactin
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31. Hormonal Changes...
• Pituitary gonadotropin production decreases
throughout pregnancy.
Adrenal gland
• The rate of adrenocortical secretion moderately increased
throughout pregnancy.
glucocorticoids (cortisol)- which is needed for maturation of
the fetal lungs (the production of surfactant)
Increase in adrenal androgens secretion
  aldosterone  reabsorb of excess sodium retain fluid,
occasionally leading to pregnancy-induced hypertension.
• Increased secretion of renin, erythropoietin, and 1,25-(OH)2D3.
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32. Hormonal Changes...
Thyroid Gland
• The thyroid gland enlarges by an average of 18%
during pregnancy.
• The enlargement is associated with an increase in the
size of the follicles.
• Increase in TBG and total T4 & T3 levels in maternal serum
throughout pregnancy.
• Enhanced I uptake by the maternal thyroid gland
Pancreas
• Hyperplasia and hypertrophy of the β cells in the islets
of Langerhans.
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33. Hormonal Changes...
• The levels of hPL & glucocorticoids rise, leading to
the insulin resistance.
• In late pregnancy, glucose ingestion results in higher
and more sustained levels of glucose and insulin but
glucagon suppression than in the non-pregnant state.
Kidneys
• Retention of salt and water.
• Cause: Increased aldosterone and estrogen.
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34. Maternal Responses to Pregnancy
• The renal blood flow and glomerular filtration rate (GFR)
increase rapidly and peak during the second trimester.
Breasts
• Enlarge and develop mature glandular structure.
• Cause: Estrogen, progesterone, prolactin, and placental
lactogen.
Blood volume: Blood volume increases
• Cause: Total erythrocyte volume is increased by
erythropoietin, and plasma volume by salt and water
retention.
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35. Maternal Responses...
• Blood volume expands by approximately 30-40%
(1.5L)
• Total red blood cell mass expands by approximately
25% .
• Plasma volume increase approximately by 40-60%
(average by 50%, from 1.4 to 1.6L)  hemodilution.
• The greater expansion in plasma typically is reflected
by decreases in Hgb up to 11g/dl and hematocrite
(Hct) levels 33%.
• There is an increased iron requirement during
pregnancy.
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36. Maternal Responses...
Circulation:
• Cardiac output increases, total peripheral resistance
decreases (vasodilation in uterus, skin, breasts, GI
tract, and kidneys).
• Due to increase in blood volumeCO slight
increase/normal in blood pressure.
Calcium balance:
• Increased parathyroid hormone and 1,25-(OH)2D3
increase Ca2+ reabsorption & absorption.
Body weight: Increases
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37. Maternal Responses...
Metabolism:
• Metabolic rate increases 15-20 % of BMR during the latter
half of pregnancy
• Plasma glucose, gluconeogenesis, and fatty acid
mobilization all increase.
• Cause: resistance to insulin due to insulin antagonism by
placental lactogen and cortisol
• Pregnant women experience an increase in appetite due to
the added nutritional demands of the fetus.
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38. Maternal Responses...
Respiration:
• Hyperventilation occurs (arterial PCO2decreases).
• Total body oxygen consumption increase by about 10–
20%.
• The total volume of air inhaled or exhaled each
minute(minute ventilation) can increase by up to 40-
50%.
• Decrease in pulmonary tidal volume by about 30%.
• Approximately 40% reduction in the expiratory
reserve because of the elevation of the diaphragm by
the enlarged uterus.
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39. Maternal Responses...
The digestive system also undergoes changes:
• A general decrease in GI tract motility can cause
constipation and delay gastric emptying time.
• Lower esophageal sphincter tone is reduced, together with
the displacement of the abdominal contents by the
pregnant uterus, results in heartburn.
• Decreased motility of the gallbladder leads to an increased
gallbladder volume and reduced emptying of bile after
meals.
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40. Parturition
• A normal human pregnancy lasts approximately 38-40
weeks, counting from the first day of the last
menstrual cycle, or approximately 36-38 weeks from
the day of ovulation and conception.
• Factors contributing to onset of parturition are:
-Progressive hormonal changes that cause increased
excitability of the uterine musculature, and
-Progressive mechanical changes.
1. Hormonal changes
Increased ratio of estrogens to progesterone.
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42. Parturition...
• The uterine muscle increases its oxytocin receptors 
increases its responsiveness to oxytocin during the last
month of pregnancy.
• The rate of oxytocin secretion considerably increased
at the time of labor.
CRH secretion by the placenta highly increase toward
the end of pregnancy.
“Women who have higher levels of CRH earlier in pregnancy
are more likely to deliver prematurely; those who have low
levels are more likely to deliver after their due date.”
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43. Parturition...
• The precise mechanism by
which CRH is regulated is
not well known but it is
inhibited by progesterone
and stimulated by estrogen
oxytocin & stress.
• CRH stimulate estrogen &
prostaglandins secretion
from placenta and uterus.
• Estrogen & prostaglandins
stimulate uterine instability.
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44. Parturition...
Effect of fetal hormones on the uterus.
• Fetus’s adrenal glands secrete large quantities of cortisol, another
possible uterine stimulant.
• Secondary to these hormone and other reasons
different paracrine substances like activin ,inhibin
,inflammatory cytokines & proteolytic enzymes
secretion increase to favour cervical ripening,
membrane rapture and separation of placenta.
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45. Parturition...
2. Mechanical factors that increase uterine contractility
Simply stretching smooth muscles usually increases their
contractility.
Stretch or Irritation of the Cervix.
• The uterine contractions during labor begin mainly at the
top of the uterine (fundus) and spread downward over the
body of the uterus.
• Intensity of contraction is great in the fundus and body of
the uterus but weak in the lower segment of the uterus
adjacent to the cervix.
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46. • In the early stage of labor, the contractions might occur
only once every 30 minutes.
• As labor progresses, the contractions finally appear as
often as once every 1 to 3 minutes, and the intensity of
contraction increases greatly.
• During pregnancy, the uterus undergoes periodic
episodes of weak and slow rhythmical contractions.

47. Onset of Labor - A Positive Feedback
Mechanism for Its Initiation
• These contractions become
progressively stronger
toward the end of
pregnancy.
• It be comes strong
contraction that start
stretching the cervix
nerve impulses through
affernt path way to
hypothalamus  release
of oxytocin uterine
contraction
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48. Onset of Labor - A Positive Feedback...
Oxytocin increases uterine contractions in two ways:
1. It acts directly on uterine smooth muscle cells to make them
contract, and
2. It stimulates the formation of prostaglandins in the decidua.
• The prostaglandins enhance the oxytocin-induced
contractions.
Abdominal muscle contractions during labor
• Pain signals originate both from the uterus and from the birth
canal elicit neurogenic reflexes in the spinal cord to the
abdominal muscles, causing intense contractions of these
muscles.
• The abdominal muscle contractions add greatly to the force that
causes expulsion of the baby.
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49. Separation and delivery of the placenta
• After birth of the baby, the uterus continues to contract
leads to separation of placenta from the walls of the uterus.
• Separation of the placenta opens the placental sinuses
and causes bleeding.
• Further uterine contraction & prostaglandins formed at
the placental separation site cause blood vessel spasm
to cease bleeding.
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50. Separation and delivery of…
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Involution of the Uterus
• During the first 4 to 5 weeks after parturition, the
uterus involutes.
• The endometrial surface (decidua) autolyzes, causing
a discharge known as lochia.
• After this time, the endometrial surface becomes re-
epithelialized and return to non-gravid size.

51. Lactation
• In general, estrogens are primarily responsible for
proliferation of the mammary ducts and progesterone
for the development of the lobules.
• During pregnancy, prolactin levels increase steadily until
term, producing full lobuloalveolar development.
• Prolactin cause the formation of milk droplets and
their secretion into the ducts after delivery.
• After the level of estrogens decrease
• Oxytocin causes contraction of the myoepithelial cells
lining the duct walls, with consequent ejection of the
milk through the nipple.
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52. Lactation...
• After birth of the baby, the basal level of prolactin
secretion returns to the non-pregnant level over the next
few weeks.
• The principal stimulus in maintaining prolactin secretion
during lactation is the sucking action of the infant.
• Each time the mother nurses her baby, nervous signals from the
nipples to the hypothalamus cause a 10- to 20-fold surge in
prolactin secretion that lasts for about 1 hour.
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54. END