Female Reproductive system

1. Reproductive system-5
Dr. Sai Sailesh Kumar G
Associate Professor
Department of Physiology
RDGMC

3. Menstrual/ uterine cycle
 The fluctuations in circulating levels of estrogen and
progesterone induce profound changes in the uterus, giving
rise to the menstrual, or uterine, cycle.
 The menstrual cycle averages 28 days.
 Although even normal adults vary considerably from this
mean.

4. Menstrual/ uterine cycle
 The uterus consists of two main layers:
1. Myometrium, the outer smooth muscle layer
2. Endometrium contains numerous blood vessels and glands.
 Estrogen stimulates growth of both the myometrium and the
endometrium.
 Estrogen also induces synthesis of progesterone receptors in the
endometrium.
 Thus, progesterone can exert an effect on the endometrium only
after it has been “primed” by estrogen.

5. Menstrual/ uterine cycle
 The menstrual cycle consists of three phases:
1. The menstrual phase.
2. The proliferative phase.
3. The secretory, or progestational, phase.

7. Menstrual phase
 Step 23: Characterized by discharge of blood and
endometrial debris from the vagina.
 By convention, the first day of menstruation is considered
the start of a new cycle.
 It coincides with the end of the ovarian luteal phase and
onset of a new follicular phase.
 The net effect of progesterone and estrogen is to prepare
the endometrium for implantation of a fertilized ovum.

8. Menstrual phase
 Degeneration of corpus luteum (If no fertilization).
 No estrogen and progesterone
 No hormonal support to endometrial glands and blood vessels.
 Release of prostaglandins.
 Vasoconstriction of endometrial vessels, disrupting the blood
supply to the endometrium.
 Reduction in O2 delivery causes death of the endometrium,
including its blood vessels.

9. Menstrual phase
 The resulting bleeding through the disintegrating vessels flushes
the dying endometrial tissue into the uterine lumen.
 Most of the uterine lining sloughs during each menstrual period
except for a deep, thin layer of epithelial cells and glands, from
which the endometrium regenerate.
 Local uterine prostaglandin also stimulates mild rhythmic
contractions of the uterine myometrium.
 These contractions help expel the blood and endometrial debris
from the uterine cavity out through the vagina as menstrual flow.

10. Dysmenorrhea
 Excessive uterine contractions caused by prostaglandin
overproduction produce the dysmenorrhea (menstrual cramps)
some women experience.
 Indomethacin appears to effectively relieve primary dysmenorrhea
and does not appear to be associated with a high incidence of side
effects.
 Indomethacin produces potent analgesic and anti-inflammatory
effects by inhibiting the synthesis of prostaglandins.

11. Menstrual phase
 The average blood loss during a single menstrual period is 50 to
150 mL.
 Blood that seeps slowly through the degenerating endometrium
clots within the uterine cavity.
 Then is acted on by fibrinolysin, a fibrin dissolver that breaks
down the fibrin forming the meshwork of the clot.
 Therefore, blood in the menstrual flow usually does not clot
because it has already clotted and the clot has been dissolved
before it passes out of the vagina.

12. Menstrual phase
 If the flow is rapid, then the clot may not be exposed to sufficient
fibrinolysin, so when the menstrual flow is most profuse, blood
clots may appear.
 In addition to the blood and endometrial debris, large numbers of
leukocytes are found in the menstrual flow.
 These white blood cells play an important defense role in helping
the raw endometrium resist infection.
 Menstruation typically lasts for about 5 to 7 days.

13. Proliferative phase
 Estrogen stimulates proliferation of epithelial cells, glands, and
blood vessels in the endometrium.
 Increasing this lining to a thickness of 3 to 5 mm.
 The estrogen dominant proliferative phase lasts from the end of
menstruation to ovulation.

14. Secretory, or Progestational, Phase
 Coincides in time with the ovarian luteal phase.
 CL secretes both estrogen and progesterone.
 Progesterone converts the thickened, estrogen-primed
endometrium to a richly vascularized, glycogen-filled tissue.
 This period is called either the secretory phase because the
endometrial glands are actively secreting glycogen into the uterine
lumen.
 If fertilization and implantation do not occur, the CL degenerates
and a new follicular phase and menstrual phase begin again.

15. Cyclical changes in cervical mucus
 In the follicular phase, under the influence of estrogen, cervical mucus
becomes abundant, clear, and thin.
 This change, occurs just before ovulation, to facilitate the passage of
sperm through the cervical canal.
 After ovulation, under the influence of progesterone from the CL, the
mucus becomes thick and sticky, essentially plugging up the cervical
opening.
 This plug offers defense mechanism, preventing bacteria (that might
threaten a possible pregnancy) from entering the uterus from the vagina.
 Sperm also cannot penetrate this thick mucus barrier.

16. Test for ovulation
1. Recording of basal body temperature:
 Basal body temperature increased around the day of ovulation
about 0.5 degrees centigrade.
 Oral temperature is recorded usually.
 Early morning before the daily work starts record the temperature

17. Test for ovulation
2. Cervical mucus:
 Cervical mucus become thinnest around the day of ovulation.
 Less cellular and more watery.
 Fern pattern is observed upon histological examination.
3. Endometrial biopsy :
 Secretory changes in the endometrium indicate presence of
functioning CL
4. Hormonal estimation:
 FSH levels
 LH levels
 Estrogen levels
5. Ultra sound examination

18. Menopause
 The cessation of a woman’s menstrual cycles at menopause
 Sometime between the ages of 45 and 55.
 Limited supply of ovarian follicles present at birth.
 Once this reservoir is depleted, ovarian cycles, and hence
menstrual cycles, cease.
 The termination of reproductive potential in a middle-aged
woman is “preprogrammed” at her own birth.

19. Fertilization
 Fertilization, the union of male and female gametes.
 occurs in the ampulla, the upper third of the oviduct.
 Thus, both the ovum and the sperm must be transported
from their gonadal site of production.
 The ovum is released into the abdominal cavity at ovulation.
 Normally, however, the oviduct quickly picks up the egg.
 Fimbriae, fingerlike projections that contract in a sweeping
motion to guide the released ovum into the oviduct.

20. Fertilization
 Within the oviduct, the ovum is rapidly propelled by
peristaltic contractions and ciliary action to the ampulla.
 Conception can take place during a limited time span each
cycle (the fertile period).
 If not fertilized, the ovum begins to disintegrate within 12 to
24 hours and is subsequently phagocytized.
 Fertilization must therefore occur within 24 hours after
ovulation.

21. Fertilization
 Sperm 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.

22. Ectopic pregnancy
 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.
 Ectopic means “out of place”
 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.

23. Ectopic pregnancy
 If this unusual pregnancy proceeds to term, the baby must
be delivered surgically because the normal vaginal exit is
not available.
 The 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.

25. Sperm transport
 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 formidable journey, sperm need the help of the
female reproductive tract.
 The cervical mucus becomes thin and watery enough to permit
sperm to penetrate only when estrogen levels are high.

26. Sperm transport
 Once sperm have entered the uterus, contractions of the
myometrium churn them around in “washing-machine” fashion.
This action quickly disperses sperm throughout the uterine cavity.
 When sperm reach the oviduct, they are propelled to the
fertilization site in the upper end of the oviduct by upward
contractions of the oviduct smooth muscle.
 These myometrial and oviduct contractions that facilitate sperm
transport are induced by the high estrogen and seminal
prostaglandins.

27. Catsper activation
 Progesterone released from follicular cells.
 Bind with receptors on surface of sperm.
 On binding, progesterone opens Calcium-permeable cation
channels called CatSper.
 The resultant, swift Calcium entry is crucial for the following
fertilization related events in sperm:
 (1) capacitation,
 (2) hyperactivated motility, and
 (3) the acrosome reaction

28. Fertilization
 165 million sperm typically deposited in a single ejaculate.
 only a few thousand make it to the site of fertilization.
 That only a very small percentage of the deposited sperm
ever reach their destination is one reason sperm
concentration must be so high (20 million/mL of semen) for
a man to be fertile.
 The other reason is that the acrosomal enzymes of many
sperm are needed to break down the barriers surrounding
the ovum.

29. Fertilization
 The sperm penetrates the corona radiata by means of membrane
bound enzymes in the surface membrane that surrounds the head.
 Sperm can penetrate the zona pellucida only after binding with
specific binding sites on the surface of this layer.
 fertilin, a plasma membrane protein on the sperm head, binds with
ZP3, a glycoprotein in the outer layer of the zona pellucida.
 Only sperm of the same species can bind to these zona pellucida
sites and pass through.
 Binding of the sperm head to ZP3 triggers the Calcium-dependent
acrosome reaction.

31. Acrosomal reaction
 Acrosomal membrane disrupts and the acrosomal enzymes are
released.
 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.
 The acrosomal enzymes digest the zona pellucida, enabling the
sperm, with its tail still beating, to tunnel a path through this
protective barrier.
 The first sperm to reach the ovum
 itself fuses with the plasma membrane of the ovum (actually a
secondary oocyte), and its head (bearing its DNA) enters the
ovum’s cytoplasm.

33. Acrosomal reaction
 The sperm’s tail is frequently lost in this process, but the
head carries the crucial genetic information.
 Sperm–egg fusion triggers a chemical change in the ovum’s
surrounding membrane that makes this outer layer
impenetrable to the entry of any more sperm.
1. inactivate the ZP3 receptors so that other sperm reaching
the zona pellucida cannot bind with it.
2. harden the zona pellucida
 block to polyspermy

34. Fertilization
 The released Calcium in the ovum cytosol triggers the
second meiotic division of the egg.
 Within an hour, the sperm and egg nuclei fuse.
 Fertilized ovum, now called a zygote.
 The victorious sperm also activates ovum enzymes
essential for the early embryonic developmental program.

35. 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.
 The zygote is not idle during this time. It rapidly undergoes a
number of mitotic cell divisions to form a solid ball of cells called
the morula.
 Meanwhile, the rising levels of progesterone CL stimulate release
of glycogen from the endometrium into the reproductive tract
lumen for use as energy by the early embryo.

37. Implantation
 About 3 to 4 days after ovulation, progesterone is being produced
in sufficient quantities to relax the oviduct constriction.
 Permits 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.

38. Implantation
 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, 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.

39. Tubal pregnancy
 Occasionally, the morula fails to descend into the uterus
 Continues to develop and implant in the lining of the oviduct.
 This leads to an ectopic tubal pregnancy, which must be terminated.
 Ninety-five percent of ectopic pregnancies are tubal pregnancies.
 Such a pregnancy can never succeed because the oviduct cannot
expand as the uterus does to accommodate the growing embryo.
 The first warning of a tubal pregnancy is pain caused by the growing
embryo stretching the oviduct.
 If not removed, the enlarging embryo will rupture the oviduct, causing
possibly lethal hemorrhage.

41. Implantation
 Endometrium is suitable for implantation about a week after
ovulation.
 Morula continues to proliferate and differentiate into a
blastocyst capable of implantation.
 The week’s delay after fertilization and before implantation
allows time for both the endometrium and the developing
embryo to prepare for implantation.

42. 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.
 The inner cell mass becomes the embryo and then fetus.
 The rest of the blastocyst serve as supportive role during
intrauterine life.
 The thin outermost layer, the trophoblast, accomplishes
implantation.

43. Implantation
 When the blastocyst is ready to implant, its surface
becomes sticky.
 By this time, the endometrium is ready to accept the early
embryo and it 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.
 The trophblastic cells overlying the inner cell mass release
protein digesting enzymes.

44. Implantation
 These enzymes 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 cell.
 Trophoblast cells – helps for implantation and also makes
metabolic fuel and raw materials available for the developing
embryo.
 Trophoblastic cells degenerate, forming a multinucleated
syncytium that eventually becomes the fetal portion of the
placenta.

45. Decidua
 Stimulated by the invading trophoblast, the 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.

46. Implantation
 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.
 The trophoblastic layer continues to digest the surrounding
decidual cells, providing energy for the embryo until the
placenta develops.

47. Think!
 What prevents the mother from immunologically rejecting
the embryo–fetus, which is actually a “foreigner” to the
mother’s immune system?

48. Implantation
 Trophoblast cells produce FAS ligand
 It binds to FAS site of cytotoxic T cells
 Fas, a specialized receptor on the surface of T cells
 Initiation of apoptosis of cytotoxic T cells

49. Formation of placenta
 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.

51. Formation of placenta
 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.

52. Formation of placenta
 Soon the developing embryo sends out capillaries into
these chorionic projections to form placental villi.
 Each placental villus contains embryonic (later fetal)
capillaries surrounded by a thin layer of chorion
 Maternal and fetal blood do not actually mingle, but the
barrier between them is extremely thin.
 To visualize this relationship, think of your hands (the fetal
capillary blood vessels) in rubber gloves (the chorionic
tissue) immersed in water (the pool of maternal blood).
 Only the rubber gloves separate your hands from the water

53. Formation of placenta
 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.
 When fully developed, the placental interface for exchange
between mother and fetus would be more than 12 m2if
stretched out flat.
 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.

54. Formation of Amnion
 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.
 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
 Similar in composition to normal ECF, surrounds and cushions the
fetus throughout gestation

55. Functions of placenta
1. Respiratory function:
 Acts as fetal lung
 Supply oxygen
 Removal of Co2
 Double Bohr effect
2. Excretory function:
 Fetal kidney is non functional
 Excretion of metabolic wastages like urea, uric acid,
creatinine from fetus to maternal blood

56. Functions of placenta
3. Nutritive function:
 Diffusion of glucose, free fatty acids from maternal blood to
fetal blood
 Placenta acts as fetal liver and synthesize proteins
 Most of proteins can not cross placenta
4. Protective function:
 Prevent transportation of certain bacteria and virus
 Prevents infection to fetus
5. Endocrine function: Secretes hCG, Estrogen, Progesterone
and HCS

57. Role of hCG
 The secretion rate of hCG increases rapidly during early
pregnancy to save the CL from demise.
 This hormone, which is similar to LH and binds to the same
receptor as LH, stimulates and maintains the CL so that it
does not degenerate.
 Now called the corpus luteum of pregnancy,
 Till placenta become capable to secrete adequate amount of
E and P
 It takes about 3 months for placenta to secrete required
amounts of E and P for maintenance of pregnancy.

58. Role of hCG
 Human chorionic gonadotropin is eliminated from the body
in the urine.
 Pregnancy diagnosis tests can detect hCG in urine as early
as the first month of pregnancy.
 about 2 weeks after the first missed menstrual period,
 the test permits early confirmation of pregnancy.

59. Morning sickness
 A frequent early clinical sign of pregnancy is morning
sickness.
 A 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.
 hCGmay trigger the symptoms, perhaps by acting on the
chemoreceptor trigger zone next to the vomiting center.

61. Preventing Ovulation
 Oral contraceptives, or birth control pills
 available only by prescription
 prevent ovulation primarily by suppressing gonadotropin
secretion
 synthetic estrogen like and progesterone like steroids
 are taken for three weeks
 and then are withdrawn for one week
 inhibit kisspeptin and GnRH and thus FSH and LH secretion.
 follicle maturation and ovulation do not take place
 so conception is impossible

62. Preventing Ovulation
 long-acting subcutaneous (“under the skin”) implantation of
hormone-containing capsules that gradually release
hormones.
 at a nearly steady rate for five years.
 birth control patches impregnated with hormones that are
absorbed through the skin.
 Oral contraceptives have been shown to increase the risk of
intravascular clotting.

63. Blocking implantation
 Blocking implantation is most commonly accomplished by a
physician
 inserting a small intrauterine device (IUD) into the uterus.
 The presence of this foreign object in the uterus
 induces a local inflammatory response
 that prevents implantation of a fertilized ovum.

64. Emergency contraception
 preventing pregnancy if used within the immediate days
following unplanned unprotected sexual intercourse.
 for emergency use only
 if a condom breaks or in the case of rape
 should not be used as a substitute for ongoing
contraceptive methods
 The two means of emergency contraception are taking
morning after pills and insertion of a copper IUD

65. Emergency contraception
 morning-after pills must be taken within 3 days (not just the
morning after) or
 an IUD must be inserted within 5 days.
 Morning after pill- high concentration of estrogen/ progesterone/
both
 Morning after pill prevents ovulation or
 prevent fertilization by suppressing sperm motility
 It can irritate the lining of the uterus (endometrium) so as to inhibit
implantation.
 An alternative nonhormonal morning-after pill (Ella), available by
 prescription only, is a progesterone receptor modulator that
delays or inhibits ovulation

66. Immunocontraception
 the use of vaccines that prod the immune system to
produce antibodies targeted against a particular protein
critical to the reproductive process.
 The contraceptive effects of the vaccines are expected to
last about a year.
 in the testing stage.

67. Terminating unwanted pregnancy
 When contraceptive practices fail or are not used and an
unwanted pregnancy results, women often turn to abortion
to terminate the pregnancy.
 Medical termination of pregnancy
 Abortion in India has been legal under various
circumstances for the last 50 years with the introduction of
Medical Termination of Pregnancy (MTP) Act in 1971.
 Abortion can now be performed until 24 weeks pregnancy
as the MTP Amendment Act 2021 has come in force by
notification in Gazzette from 24th September 2021.

69. THANK YOU