FERTILIZATION AND PREGNANCY 2023.pptx

A BRIEF INTRODUCTION ON FERTILIZATION IN HUMANS

1. FERTILIZATION AND PREGNANCY DR JOSHUA TUGUMISIRIZE YEAR 2 , DECEMBER 2023

2. OBJECTIVES 1 The process of fertilization, implantation and recognition of pregnancy 2 The formation and function of the placenta 3 Placental hormones and maintenance of pregnancy 4 Major physiological changes during pregnancy 5The mechanism of partition 6 Lactation

3. OPTIMAL CONDITIONS FOR PREGNANCY The male must be capable of ejaculation of viable and adequate sperms The female must be able to ovulate The timing of sexual intercourse must be within the window – five days around the time of ovulation: the ovum is viable for 24 hours; the sperm is at best within 24 to 48 hours, but in the extreme, could be viable over 5 days. We can predict the period of ovulation- 14 days before the next menstruation

4. SPERMS IN THE VAGINA Prostaglandins in seminal fluid make the cervical mucus permeable to sperms Prostaglandins induce retrograde movements in uterus and fallopian tubes – transport sperms to site of fertilization The alkaline secretion from prostate gland serves to neutralize the acid (pH 3.5 – 4.0) in the vagina to pH 6.0- 6.5. Sperms become optimal motile in a less acid medium A few sperms perform the journey in 5 minutes!

5. SPERM MOTILITY Progressive motility is the ability of the sperm to move forward This is made possible by activation of CatSper , a protein found in the principle piece of the sperm tail. CatSper is a Ca2+ channel, which permits cAMP generalized influx.

6. THE SPERM

7. CAPACITATION Process that prepares the sperms to penetrate the zona pellucida of the oocyte Bicarbonate – activation of soluble adenylyl cyclase and increase of cAMP ; activation of PKA Protein phosphorylation – loss of plasma membrane cholesterol (cholesterol is washed away) Rearrangement of membrane lipids Membrane of sperm more permeable to calcium Entry of calcium into sperm – release of enzymes to enable penetration of the oocyte (acrosome reaction)

8. ACROSOME REACTION Sperm has hyaluronidase and proteolytic enzymes They break down proteins in the wall of the ovum- to dissolute the layer of granulosa cells Enzymes in the head of sperm are released to help penetrate the zona pellucida ? Fertilin Role of nitric oxide and Ca++

9. ACROSOME REACTION Sperm has hyaluronidase and proteolytic enzymes The break down proteins in the wall of the ovum- to dissolute the layer of granulosa cells Enzymes in the head of sperm are released to help penetrate the zona pellucida

10. THE OVARIA CYCLE

11. OVULATION

12. MATURATION OF OVUM Primary oocyte- this is before the first meiotic division Secondary oocyte- shortly before release from ovarian follicle, the nucleus divides by meiosis. The first polar body is expelled from the nucleus The secondary oocyte has 23 chromosomes (22 +X)

13. OVUM IN PERITONIAL CAVITY Corona radiata - a hundred or more granulosa cells surround the ovum to form the corona radiate Cilia of the fambriated tentacles lined with cilia- activated by estrogen from the ovary, beat toward the opening or ostium of the fallopian tube The ovum carried into fallopian tube in a slow fluid current 98% of the times the ovum will find the way into the fallopian tube. The ovum can even find its way to the fallopian tube on the opposite site

14. TRANSITION PERIOD The ovum must find its way to the uterus The sperm must find the ovum within the fallopian tube. Success rate is very high. Small percentage of ectopic pregnancies – e g abdominal pregnancy There is evidence of chemotaxis : the ova produce a chemical that attracts the sperms- allurin – is similar to olfactory receptor hOR12-4

15. HOW SPERMS TRAVEL TO SITE OF FERTILIZATION Rate: 1-4 mm/min; Prostaglandins from seminal fluid and oxytocin, releases from posterior pituitary gland of the female at orgasm, cause contraction of uterus and fallopian tubes A few sperms take 5 to 10 minutes to arrive in the ampullae , where they normally meet the ovum and where fertilization normally takes place. In the end 50 to 100 sperms reach the ovum and many of these make contact with the zona pellucida

16. SPERMS AND CHEMOTAXIS Sperms travel through the vagina to the fallopian tube Movement pf sperms aided by chemoattractant substances secreted by the Ovary

17. SITE OF FERTILIZATION The ovum is expelled into the peritoneal cavity It must enter the fallopian tube so it can be transport to the uterus. The fambrie at the end of the fallopian tubes fall around the ovaries. They are ciliated. The cilia are activated by estrogen from the ovaries. The cilia beat towards the opening of the fallopian tubes. Up to 98% of ova succeed to enter fallopian tubes.

18. ROLE OF OXYTOCIN Stimulation of the nipples , vagina and cervix leads to secretion of oxytocin. In a non-pregnant woman, oxytocin stimulates contraction of uterine muscles, and anti-peristalsis in fallopian tubes. These two actions aid in transport of sperms to the site of fertilization

19. WHAT CAN GO WRONG WITH SPERMS Azoospermia- lack of sperms in semen. A congenital disease OR can result from excessive use of corticosteroids and androgens Oligozoospermia – low sperm count, less than 20 million/ml Teratozoospermia : presence of sperms with abnormal morphology Oligospermia – low semen volume

20. TO SHOW AMPULLA

21. FERTILIZATION SITE

22. FERTLIZATION AND AFTER

23. TRANSITION STAGE BEFORE ZYGOTE

24. TIMELINES A few sperms can reach the ampulla in 5 to10 minutes Fertilization within 24 hours of release of ovum Travel from tube to uterus, 3 – 4 days Implantation by day 7 after ovulation

25. THE PROCESS OF FERTILIZATION

26. FERTILISATION 1

27. ALTERNATIVE PRESENTATION OF FERTILIZATION

28. FERTILIZATION 3

29. FERTILIZATION 4 & 5

30. FERTILIZATION 6

31. ONLY ONE SPERM PERMITTED INTO THE OVUM Not completely true When the sperm penetrates the zona pellucida , calcium ions diffuse inwards, multiple cortical granules break down- release chemicals that spread in the perivetelline space and block entry of more sperms. Calcium is involved in this process. Release of cortical granules takes place after calcium entry into the oocyte Occasionally more than one sperm are able to penetrate into the oocyte - non-identical twins or ???

32. THE ZYGOTE The male pronucleus and the female pronucleus , each with 23 unpaired chromosomes become aligned , and form a complete complement of 46 chromosomes (23 pairs) in the fertilized ovum or zygote.

33. FULL COMPLEMENT OF CHROMOSOMES

34. SEX DETERMINATION From the female: ovum, which may contain X From the male: sperms; either X or Y Possible combinations: XX- female; XY- male

35. A CASE FOR MULTIPLE PREGNANCIES Identical twins- one fertilized egg splits in two during mitosis, and before implanation . Same genes Fraternal twins- two eggs fertilized separately Three or more More than two usually result of in vitro fertilization Woman in USA 2009- 8 children, who all survived Halima Cisse , 25,from Mali, May, this year gave birth to 9 babies

36. TIME LINES From fertilization, the zygote, travels to the uterus Takes 3 to 5 days to complete journey At entry into the uterus, the zygote is a call of about 100 cells (the blastocyst)

37. THE JOURNEY OF ZYGOTE TO THE UTERUS

38. *BLASTOCYST

39. THE BLASTOCYST Stays 1 to 3 days before implantation Nutritional needs are met by ‘uterine milk’, the secretions from the endometrium A trophoblast, made up of cells that develop over the surface of the blastocyst. These cells secrete proteolytic enzymes that will digest and liquefy the adjacent cells of the endometrium

40. *IMPLANTATION Role of trophoblast: proteolytic enzymes which digest and liquefy the cells in the uterine endometrium Subsequently the trophoblasts proliferate and form the placenta Production of human chorionic gonadotropin ( hCG ) – earliest 7 days in blood; 10- 12 days in urine. Indicator of successful implantation hCG enables continuation of corpus luteum, and production of estrogen and progesterone

41. PLACENTA Early formation and secretion- day 16; fully functioning placenta by week 8 Functions: 1 supply oxygen to foetus 2 remove of carbon dioxide from the fetus 3 supply nutrients to the foetus 4 remove waste from the fetus 5 secrete hormones: placental hCG , estrogen , progesterone, human chorionic somatommatropin hcs ’ and relaxin

42. FETAL HEART 21 days after fertilization blood begins to be pumped by the heart of the human embryo. Blood sinuses are supplied with blood from the mother, outside the trophoblastic cords Trophoblastic cells send more projections – which become placenta villi, into which fetal capillaries grow. That is-the villi carrying fetal blood are surrounded by sinuses carrying maternal blood.

43. FORMATION OF PLACENTA 1

44. IMPLANTATION 2

45. FORMATION OF PLACENTA 3

46. FORMATION OF PLACENTA 4

47. MATURE PLACENTA AND FETUS

48. COMPONENTS OF PLACENTA

49. EMBRYONIC DISK

50. EMBRYONIC DISK AND A PRIMITIVE STREAK

51. FIRST TRIMESTER Sustained by hormonal production from corpus luteum Critical period because the embryo may rejected or expelled Deficiency of hCG in the first 2 months of pregnancy results in abortion because of involution of corpus luteum hCG stimulates development of testes

52. PREGNANCY TESTS The old biological methods were based on injection hCG into a test animal The modern immunological methods are rapid and simple to perform: rabbit antibodies against hCG Positive on day 7 if blood is used Positive on day 10 if urine is used

53. IMMUNOLOGICAL TEST OF PREGNANCY

54. ABORTION One in five women experience bleeding or spotting in the first 12 weeks of pregnancy Prolonged bleeding portends miscarriage Inserting progesterone into the vagina twice a day may avert an abortion ( micarriage ) Prof Arri Coomarasamy for The university of Birmingham About 1 in 4 pregnancies end in miscarriage

55. THE PLECENTA’S FUNCTION IN SECOND AND THIRD TRIMESTERS The placenta takes over the role of the corpus luteum The major function of the placenta is to provide for diffusion of foodstuffs and oxygen from the mother’s blood into the fetus’s blood and diffusion of excretory products from the fetus back into the mother. The surface area is small. Permeability is initially low (thick membrane) Late in pregnancy, the membrane becomes thinner and permeability increases. The surface area increases many times over!

56. BLOOD FLOW Blood of the fetus flows through two umblical arteries into the capillaries of villi. Blood flows back into the fetus through a single umbilical vein The mother’s blood flows from the uterine arteries into large maternal sinuses that surround the villi. Blood flows back to the mother through the uterine veins

57. PERFUSSION ACROSSPLACENTAL MEMBRANE DURING PREGNANCY

58. GASEOUS EXCHANGE IN PLACENTA Mother Arterial end: pO2 96 mmHg, pCO2 40 mmHg Venous end: pO2 42mmHg, pCO2 46 mmHg Fetus : umbilical artery: pO2 16 mmHg, p CO2 55mmHg Umbilical vein: pO2 29 mmHg, pCO2 41 mmHg

59. GASEOUS TRANSPORT ACROSS PLACENTA Maternal blood pO2 about 50 mmHg Foetal blood pO2 about 20 mmHg Foetal Hb carries 20- 50% more oxygen than adult Hb The total diffusion capacity of the entire placenta for oxygen is 1.2 ml of oxygen per minute per mmHg oxygen pressure difference across the membrane

60. pCO2 The gradient for exchange of CO2 is 3 mmHg. This is sufficient because CO2 is highly soluble Fetal blood easily gives carbon dioxide to maternal blood (Bohr effect) CO2 is extremely soluble. It diffuse 20 times as fast as oxygen across the placental membrane .

61. BOHR EFFECT

62. EXPLAINING THE BOHR EFFECT Haemoglobin carry more oxygen at low pCO2 than at high pCO2. Fetal blood entering the placenta carries large amounts of carbon dioxide , but much of the carbon dioxide diffuses from the fetal blood into maternal blood. Loss of carbon dioxide makes fetal blood more alkaline whereas increased carbon dioxide in maternal blood makes more acidic. These changes increase the capacity of fetal blood to combine with oxygen and decrease oxygen binding capacity of maternal blood which forces still more oxygen from maternal blood which enhances oxygen uptake by the fetal blood- The Bohr effect operates one direction in maternal blood, and in another direction in fetal blood. These two effects make the Bohr effect twice as important as it is for gaseous exchange in the lungs- double Bohr effect

63. PLACENTAL EXCHANGE OF NUTRIENTS AND WASTE There is facilitated diffusion of glucose . Glucose is carried by transporter molecule - GLUT1. However, glucose level in fetal blood is 20-30% lower than maternal glucose level Active transport of amino acids High solublity of fatty acids across placental membrane. Nevertheless fatty acids diffuse from maternal blood to fetus more slowly than glucose. So the fetus used more glucose than fatty acids Ketone bodies, potassium , sodium and chloride diffuse with relative ease from the maternal blood into fetal blood Excretion of urea and bilirubin Is the placenta protective? Immunilogical barrier?

64. EXCRETION OF WASTE PRODUCTS Nitrogenous products include urea, uric acid and creatinine Urea levels in fetal blood slightly higher than in maternal blood because urea diffuses across placental membrane with great ease. Creatinine does not diffuse easily. There are higher levels in fetal blood

65. HORMONAL FACTORS Key hormones : human chorionic gonadotropin ( hCG ), Estrogens, progesterone and human somatomammotropin ( hCM ) hCG from the syncyotrophoblast ; prevents menstruation: sustains the implanted embryo hCG first measured in blood 8 to 9 days after fertilization. Secretion rises to the maximum about 10- 2 weeks of pregnancy and decreases to lower values by 16 to 20 weeks. It continues at this level through the pregnancy

66. hCG hCG molecular weight of 39,000; same molecular structure and function as LH from the pituitary gland Most important function is to prevent involution of the corpus luteum. It causes the corpus luteum secrete large quantities of sex hormones- progesterone and estrogens. The hormones prevent menstruation They cause growth of the endometrium –into decidual cells to provide nutrition for the implanted embryo If corpus luteum is removed before the 7 th week pregnancy (sometimes before the 12 week) spontaneous abortion occurs After 12 th week, the placenta produces enough progesterone and estrogen to sustain the pregnancy. The corpus luteum, involutes after the 13 th to 17 th week of gestation

67. hCG AND TESTOSTERONE In a male fetus, hCG stimulates the fetal tastes to produce testosterone. Production of testosterone is sustained until after birth Testosterone is responsible the growth and development of the male fetus. It is also responsible for descent of testes into the scrotum near the end of pregnancy (last 2 to 3 months)

68. ESTROGENS Estrogens in the placenta are formed almost entirely from androgens – dehyroepiandrosterone and 16-hydroxydehydroepiandrosterone, which are formed in the mother’s adrenal glands and the fetus’s adrenal glands These weak androgens are transported by the blood to the placenta They are converted into estrogens by the trophoblast cells into estradiol, estrone and estriol The cortices of the fetal adrenal glands are extremely large. 80% consist of fetal zone- the primary function of the fetal zone is to secrete dehydroepiandrosterone during pregnancy

69. PLACENTA AS AN ENDOCRINE ORGAN

70. INTERACTION BETWEEN PLACENTA AND FETAL ADRENAL

71. HORMONAL INFLUENCES ON PREGNANCY

72. From GUYTON

73. HORMONAL CHANGES DURING PRGNANCY

74. HORMONAL CHNGES ACROSS PREGNANCY

75. CHANGES DURING PREGNANCY The pituitary gland increase in size by 50%. Along with this, is increased production of ACTH, TSH, Prolactin Because of inhibitory effects of estrogen and progesterone, FSH and LH are hardly produced ACTH leads to increased production of glucocorticoids and aldosterone Glucocorticoids mobilize amino acids from the mother for use in the fetus. Aldosterone levels are almost double. This is responsible for increased retention of water and sodium ( increased blood volume )

76. THYROID GLAND Increased TSH leads to enlarged thyroid gland (by 50%). There is increased thyroid hormones from this source Secondly placental hCG and human chorionic thyrotropin are in part responsible increase in thyroid hormones

77. PARATHYROID GLAND Enlargement is dependent on levels of calcium levels. In cases there is low calcium, the parathyroid gland will respond and enlarge. This leads to absorption of calcium During lactation more calcium is absorbed to meet the needs of the mother and the baby

78. HORMONE LEVELS IN MATERNAL BLOOD DURING PREGNANCY

79. FUNCTION OF ESTROGEN IN PREGNANCY 1 Enlargement of the mother’s uterus 2 Enlargement of the mother’s breasts and growth of ductal structure 3 enlargement of the mother’s female external genitalia 4 Estrogens relax the pelvic ligaments of the mother. Make passage of the fetus easier during birth 5 Estrogens affect rate of cell production in early embryo

80. PROGESTERONE 1 Moderate amounts produced by corpus luteum 2 Large amounts produced by the placenta Functions: 1 development of decidual cells in uterine endometrium, to provide nutrition to the embryo 2 Decrease the contractility of the pregnant uterus. Prevents uterine contractions from causing spontaneous abortion 3 Provide nutrition for embryo-secretions from the uterus and fallopian tubes – for morula – 16- 32 cell, before the blastula and blastocyst) 4 progesterone affect cell cleavage in the early embyro development 5 Helps estrogen prepare breasts for lactation

81. BLOOD VOLUME

82. CHANGE IN WEIGHT During pregnancy the mother may put on an average of 2 kg. Many factors are involved e g access to food; access to support; maintenance of good physical and psychological health BMR increases by 15% Fetus 3.5 kg Amniotic fluid ?2kg Placenta 1.5 kg Maternal body weight 5.0 kg

83. CHANGES cont’d Cardiac out put 4.5- 6.0 L/min Stroke volume increases by 10% Heart rate from 70 to 80- 90 per min Plasma volume increases by 50% RBCs increase by 30% Drop in Hb from 3 to 12 gm/dl Enlarged pituitary gland

84. UNDESCENDED TESTIS Failure of one or both testis to descend from abdomen to scrotum. Descent is promoted by testosterone and gonadotropic secreted by Leydig cells The inguinal canal must be open If left untreated -they lead degeneration of seminiferous tubules and infertility -they are prone to cancer Surgery may be required

85. MECHANICAL FACTORS IN PARTRITION

86. PARTURITION The estrogen /progesterone ration increases Increased stretching of the uterine wall Stretching of the cervical canal Release of oxytocin , increased oxytocin receptors Increased sensitivity of the uterine muscles to the hormones

87. OXYTOCIN AND PARTURITION

88. CONTRACEPTION Prevention of pregnancy, by choice Make sure sperms do not meet ovum- put barriers Prevent ovulation: pills Prevent implantation: coil

89. CONDOM

90. INTRAUTERINE DEVICE

91. INFERTILITY 1 5-10% women are unable to conceive -genetic -abnormal physiology Failure to ovulate- thick ovarian capsule Hypersecretion of gonadotropic hormones Endometriosis Abnormal mucus Infections

92. INFERTILITY 1 5-10% women are unable to conceive -genetic -abnormal physiology Failure to ovulate- thick ovarian capsule Hypersecretion of gonadotropic hormones Endometriosis Abnormal mucus Infections

93. INFERTILITY 2 The male factor Low sperm count or no sperms Undescended testis Abnormal conditions for spermatogenesis – Drugs Infections and trauma- mumps

94. CONTRACEPTION/FERTILITY CONTROL Rhythm method: take into account that ovum viable for 24 hours; sperms viable for 24- 48 hours. Safe period: 4- 5 days after menstrual bleeding and 5 to 6 days before the start of the next period Too much depends of self restraint Mechanical Barriers: prevent sperms from entering the uterus – Male condom; female: diaphragm or cervical cap Chemical: spermicidal cehemicals , jellies ete ; pills

95. CONTRACEPTIVE PILLS Pills inhibit maturation of follicles and ovulation There are different types of pills, based on specific hormones or combination of hormones Synthetic estrogens: ethinyl estradiol or mestranol Synthetic progesterone: norethindrone , or norgestrol The hormones prevent secretion of FSH and LH Progesterone increases the thickness of cervical mucus which prevents entry of sperms into the uterus

96. TYPES OF PILLS There are different types of pills The mechanism of actions Adverse effects and complications of use of pills -clotting tendencies -hypertension, heart attacks ; increased risk of stroke - Increased risk of cancer (breast)

97. IUCD/SURGERY Prevention of fertilization- IUCD /copper, Lippes loop Tubal ligation Vasectomy

98. SUMMARY OF CONTRACETIVE METHODS