ERECTION, EJACULATION, AND ERECTILE DYSFUNCTION.pptx

A BRIEF INTRODUCTION ON MALE SEXUAL ENDOCRINE FUNCTION.

1. GAMETOGENESIS, FERTILZATION AND PREGNANCY Dr JOSHUA TUGUMISIRIZE Ph. D 2023

2. OBJECTIVES 1 Review the process of sex determination 2 Describe gametogenesis 3 The human sexual response – delivery of sperms into the female genital tract (natural vs artificial delivery processes 4 The processes leading to fertilization 5 Implantation and formation of the placenta 6 Physiological changes during pregnancy

3. CONTEXT How can we ensure the survival of species? How can we as individuals contribute to the gene pool? Transgenerational transmission of values – are there people who might opt out? Transgender? Homosexuals and Lesbians? Eunuchs? Politically? Accidental?

4. HUMAN REPRODUCTION The essence of human reproduction is for the gametes from the male and female to fuse and develop and differentiate into a ‘new’ human being Until recently, this was only possible through sexual intercourse between a mature man and a mature woman Today, we can make babies without sexual intercourse, through test tube babies (in-vitro fertilization), and surrogate mothers

5. FORMATION OF GAMETES We have already covered the gametogenesis in the female We next need to review gametogenesis in the male Remember, the gametes form through the process of meiosis. First- formation of primary germ cell Second to produce the mature gametes What are polar bodies?

6. FERTILITY A man must produce viable sperms, lots of them- 35 ml (2- 6 ml), each ml with 35-200 million sperms (average of 120million per ml) We need one sperm to make a baby; there is sperm competition: survival of the fittest in evolutionary sense The woman must produce at least one ovum every menstrual cycle Although only one sperm is required to make a baby, a male who produces less than 20 million/ml is likely to be infertile

7. GAMETES For the man: sperms For the woman: ovum (oocyte) Haploid: 22 somatic chromosomes, one sex chromosome, either X or Y

8. MALE GAMETOGESIS 1 Recall that the gonadotrophins are the same for the male and female: FSH and LH The difference resides in the target organs In the male: testis (seminiferous tubules and leydig cells) In the female: the ovary ( primodial follicles)

9. MALE GAMETOGENESIS 2 Spermatogenesis takes place in the seminiferous tubules The cells: the Sertoli cells are the factory for sperms Leydig cells produce hormones, testosterone/ inhibin that regulate spermatogenesis It takes 74 days for sperm cells to be produced About 50 of the days are spent in the seminiferous tubules

10. SPERMATOGENESIS 3 Spermatogonia or germs cells close to basal lamina The germs cells mature into primary spermatocytes (during adolescence) Primary spermatocytes under go meiotic divisions, a two stage process Secondary spermatocytes divide into spermatids (haploid number of chromosomes) The spermatids mature into spermatozoa (sperms) From a single spermatogomium , 512 spermatids will formed The descendants of a single spermatogomium remain tied together by cytoplasmic bridges until the late spermatid stage

11. TESTIS

12. STRUCTURAL DETAILS

13. SERTOLI CELLS

14. MALE

15. STAGES OF DEVELOPMENT OF SPERMS

16. BLOOD-TESTIS BARRIER

17. STAGES OF SPERMATOGENESIS-

18. THE SPERM

19. ACROSOME Thick cup-like structure Covers anterior two-thirds of the head It contains a number of enzymes ( hyaluronidase, proteolytic enzymes and acid phosphatase) which help the sperm to penetrate the ovum during fertilization

20. HORMONAL INFLUENCE ON SPERMATOGENESIS

21. MALE DEVELOPMENT AND TESTOSTERONE

22. ROLE OF HORMONES IN SPERMATOGENESIS

23. HYPOTHALAMO-PITUITARY OVARIAN AXIS

24. ALTERNATIVE VERSION

25. THE FATE OF TESTOSTERONE

26. HORMONAL INTERACTION BETWEEN LAYDIG AND SERTOLI CELLS

27. LH AND FSH FSH and LH each contains two polypeptides α and β . These hormones contain identical α subunit but different β subunits Each hormone is glycosylated before release into circulation. Glycosylation regulates the half-life, protein folding for receptor recognition, and for biological activity LH and FSH bind the G-protein -coupled receptors on Leydig and Sertoli cells and increase cAMP cAMP accounts for most of the actions of LH and FSH on testicular cells ((PKA- mediated activation of transcription factors such as a steroigenic factor -1 (SF-1) and cAMP response element –binding protein (CREB))

28. TESTES They are stimulated by LH and FSH to produce sperms and regulatory proteins- activing, androgen-binding protein (ABP), follistatin and inhibin

29. GnRH SECRETED IN PULSATILE MANNER For proper functioning of the hypothalamogonadal system, GnRH must released in a pulsatile manner. The pulsatile of GnRH release serves an important physiological function LH and FSH are also released in a pulsatile manner Low -frequency GNRH pulses lead to FSH release; high-frequency gNRH pulses stimulate LH release Continuous exposure of gonadotrophs to GnRH results in desensitization of GnRH receptors leading to a decrease in LH and FSH secretion

30. EFFECT OF GnRH PULSATILE RELEASE

31. TESTOSTERONE

32. EUNUCHOID MAN Hypogonadal EUNUCHOID men exhibit low levels of LH in serum and do not exhibit pulsatile secretion of LH Pulsatile injections of GnRH restore LH and FSH secretion and increase sperm count

33. DESCENT OF TESTES Embryonic stage: testes lie attached to the posterior abdominal wall When the embryo elongates- the testes move to the inguinal ring Between 7 th month of pregnancy and birth, the testes descend through the inguinal canal to the scrotum Optimal temperature for production of sperm is 2 to 3 degrees celcius lower than he core body temperature The location of the testes in the scrotum allows for this Cooling of the testes: pampiniform plexus of blood vessels, serve as countercurrent heat exchanger between warm arterial blood reaching the testes and cooler venous blood leaving the testes. The second is the cremasteric muscle which responds to changes in temperature by moving the testes closer or farther away from the body Sustained exposure of testes to body temperature leads to failure pf spermatogenesis

34. AROMATASE Sertoli cells secrete androgen binding protein (ABP) and inhibin They do not synthesize androgens, but contain aromatase, the enzyme responsible for conversion of androgens to estrogens

35. TESTOSTERONE Testosterone is produced at the rate of 4-9mg/day ( 13.9- 31.33 µ mol /day) 98% of testosterone in plasma is bound to protein: 65% is bound to a β -globulin called gonadal steroid –binding globulin (GBG) or sex steroid-binding globulin and 33 % bound to albumin. Plasma level of testosterone level (free and bound ) is 300- 1000 ng/ dL (10..4- 34.7 nmol /L) in adult men compared to 30-to 30 ng/ dL (1.04- 2.43 nmol /L) in adult women

36. DIHYDROTESTOSTERONE (DHT) Formed in testes by action of 5 α -reductase (from Sertoli cells) on testosterone (from Leydig cells) About 80% of dihydrotestosterone is derived from peripheral conversion of testosterone in the skin (prostate gland, seminal vesicles, epididymis) DHT has more than twice the biological activity of testosterone

37. ACTIONS OF TESTOSTERONE

38. SEXUAL INTERCOURSE The natural delivery system for the man to deposit the sperms (semen) into the female reproductive tract There other delivery methods : artificial insemination, and test tube babies

39. TESTOSTERONE RESPONSIBLE SECONDARY SEXUAL CHARACTERISTS IN MALES

40. HUMAN SEXUAL RESPONSE CYCLE

41. SEXUAL AROUSAL The stimuli are many. The process is initiated : arousal phase Stimulation of sensory nerves in the glans penis. There are special modality of sensation called sexual sensation Signal from the glans penis to the spinal cord along the pudendal nerve This leads to excitement: erection The act of intercourse leads to plateau and orgasm and ejaculation The job is done! Then Resolution follows There is an interval – variable in length before the next cycle.

42. MODE OF STIMULATION Slippery massing action of intercourse on the glans (rhythmic massage of penis) Sexual signals up the pudendal nerve to sacral plexus, to sacral portion of cord and up to the brain Other sources of sexual stimuli: anal epithelium, the scrotum, the perineal structures Sensations from internal structures: urethra, bladder, prostate, seminal vesicles, testes and van deferens Mild inflammation may enhance stimulus pleasure Aphrodisiac drugs may arouse through irritation of bladder and urethra or through vascular congestion .

43. PSYCHIC ELEMENT OF MALE SEXUAL STIMULATION Sights, sound, odour Thinking about it Dreaming about it BUT worry and stress and depression may take away the interest

44. SPINAL CENTRE Integration centres for reflexogenic erection are L2 – L3 and sacral segments S2-S4 Erection: parasympathetic- S 2- S4 Ejaculation: sympathetic: T11- L 2 (??)(Lumber centre L2-L4) Stimuli: local / mechanical plus psychological Sights, sounds, smells, erogenous touch (pleasuring), kissing (love making!) What is the definition of Romance?

45. SPERM DELIVERY SYSTEM

46. NEURAL CONTROL OF ERECTION 1

47. NEURAL CONTROL OF ERECTION 2

48. NITRIC OXIDE

49. ERECTILE TISSUE OF THE PENIS

50. NEURAL CONTROL OF ERECTION

51. THE FEMALE SEX/ GENDER These days one has to be careful when describing sex role (or gender roles) What is transgender? Lesbian? Gay? Homosexual? We must address pleasure as an activity and as a life style choice. Reproduction is a matter of survival of species and not a FAD!!!

52. EJACULATION Ejaculation has two parts 1 Emission – movement of semen into the urethra 2 Ejaculation proper- propulsion of semen out of the urethra The reflex: 1 afferents from the touch receptors in the glans penis go via the pudendal nerves to spinal cord 2 Efferents via sympathetic fibres from the lumber segmements , via hypogastric nerves to vas deferens , seminal vesicles The somatic component of the reflex is by internal pudendal nerves

53. SEMEN 10% sperm from vas deferens 60% fluid from seminal vesicles 30% fluid from prostate glands pH 7.5 Prostate secretion: clotting enzymes, fibrinolysin , Seminal secretion: fructose, citric acid; fibrinogen, prostaglandins; Prostaglandins – assist sperms in penetrating cervical mucus and through influence on peristalsis in uterus and fallopian tube move the sperms towards the ovary Prostate secretions contain : calcium, citrate ion phosphate ion, clotting enzymes and a profibrinolysin .

54. COMPOSITION OF SEMEN

55. SPERM

56. SPERMATOGENESIS

57. SEXUAL EXCITEMENT IN FEMALE Glands in the vestibule secrete mucus Large amount of mucus as exudate from the walls of the vagina The secretions provide lubrication that allows easy entry of the penis into the vagina Tactile stimulation Triggering of orgasm Events signaling orgasm: vaginal, uterine, and perineal muscles contract rhythmically and muscle tension increases through the body There is a sense of satisfaction and relaxation Possible to experience multiple orgasms with ongoing stimulation It is not necessary to experience orgasm for fertilization to occur Some women may not enjoy intercourse at all and yet the become pregnant

58. FEMALE SEXUAL BEHAVIOUR AND THE FEMALE SEX ACT The role of hormones Androgens and possibly estrogens affect cells in the ban, especially in the hypothalamus, to influence sexual behavior In addition to hormonal effect, there are psychological factors Neural pathways –sympathetic and parasympathetic During sexual excitement- erectile tissue with the clitoris, and around the vaginal opening becomes engorged with blood as result of parasympathetic stimulation ;

59. SEXUAL STIMULATION OF FEMALE Massaging/irritation of external genetalia - vulva, clitoris, labia minora labia majora ) and perineal area Clitoris is highly sensitive and is responsible for initiation of sexual sensations Massaging the breasts; Kissing

60. MOTHERHOOD In my view, a woman, is the human being biologically and potentially, capable of pregnancy! Females undergo the same sexual response phase as a male. The difference: the female does not Ejaculate at orgasm. There are alot of myths about female orgasm. Technically, women do not deliver eggs through sexual activity!

61. FEMALE FERTILITY AND PREGNANCY Deposition of sperm cells deep into vagina The sperm cells must traverse the cervix, uterus and fallopian tube to reach the ampulla The sperm cells must swim vigorously To their aid is contraction of the uterus and fallopian tube. Prostaglandins play some role in contraction of the uterus and fallopian tubes During intercourse oxytocin is released from the posterior pituitary of the female especially so at the time of orgasm. Oxytocin stimulates smooth muscle in the uterus and fallopian tubes

62. SEMEN IN THE FEMALE GENITAL SYSTEM pH of vagina altered from acid 3.5 to 4 to become more alkaline 6.0- 6.5 Clotting enzymes from prostatic fluid causes fibrinogen from seminal fluid to form a weak coagulum Sperms trapped in the coagulum In next 15 to 30 minutes, the coagulum is dissolved by fibrinolysin from the prostate Initially sperms in the coagulum were not mobile, but become mobile as the coagulum dissolves Sperms at normal body temperature will survive for 24 to 48 hoiurs

63. CAPACITATION OF SPERM CELLS Capacitation: the process that makes a sperm fertilize an ovum. It takes 1- 10 hours While passing through the vagina, the uterus, the uterine tubes, the sperm cells undergo capacitation This involves the removal of proteins and the modification of glycoproteins of the sperm cell membranes. Following capacitation, acrosomal enzymes of some sperm cells are released as the sperm cells move the uterus and the fallopian tube The ovum can only be fertilizable up to 24 hours after ovulation, whereas some sperm cells remain viable in the female reproductive tract for up to 6 days Most sperm cells degenerate after 24 hours For fertilization to occur successfully, sexual intercourse must occur between 5 days before and I day after ovulation

64. CAPACITATION Cholerestarol content of the acrosomal membrane decreases; easy release of enzymes The membrane of sperm cells becomes permeable to calcium ions The influx of Ca++ acts by two ways It makes the flagellar movements of the sperm stronger And whipish ( hyperactivation of sperms) Secondly, it triggers the release of enzymes from the acrosome NB The protein CatSper is localized in the principal piece of the sperm tail. This protein appears to be a Ca++ ion channel that permits cAMP –generalized Ca++ influx

65. CAPACITATION Process that prepares the sperms to penetrate the zona pellucida of the oocyte Bicarbonate solution Wash away cholesterol Membrane of sperm more permeable to calcium Entry of calcium into sperm – release of enzymes to enable penetration of the oocyte

66. CAPACITATION OF SPERMS The sperm must acquire the capacity to fertilize the ovum – this is referred to as capacitation This takes 1 to 10 hours It involves washing away cholesterol that came from seminiferous tubules, Entry of calcium through the membrane of sperm; Calcium increased the activity of the flagellum of the sperm Calcium in addition facilitates the acrosome reaction

67. SPERM COUNT AND FERTILITY On coitus, the average volume of semen released is 3.5 ml Each milliliter contains 120 million sperm (range 35- 200 million/ml) An average of 400 million sperm are released in each ejaculate Infertility is most likely when an ejaculate has less than 20 million/ml Too frequent ejaculation reduces the number of sperm and may reduces the chances of fertilization

68. SPERM CELL MOVEMENT

69. ACROSOME REACTION For the sperm to penetrate the wall around the ovum, the acrosome reaction must take place. The acrosome membrane become weak, and the proteolytic enzymes and hyaluronidase in the acrosome are released. Hyaluronidase depolymerizes the hyaluronic polymers in the intercellular cement that holds the ovarian granulosa cells together. Then the proteolytic enzymes digest the enzymes in structural elements of tissue cells that still adhere to ovum. When the sperm reaches the zona pellucida , the anterior membrane of the sperm binds with receptor proteins of zona pellucida The entire acrosome rapidly dissolves and all the acrosomal enzymes are released Within 30 minutes the cell membrane of the sperm head and of the oocyte fuse with each other

70. HOW THE SPERM TARGETS THE OVUM The spermatozoa express olfactory receptors , while the ovaries produce odorant molecules There is chemotaxis- the sperms move toward the ovary

71. ‘WOMEN WITH WATERS’ Naturally, sexual intercourse should be enjoyable The woman produces fluids that make sexual intercourse smooth Fluid come from Bartholins glands, skenes glands, exudate from the clitoral tissue, exudate from vaginal walls and some mucus and fluids from the cervix Some women deliberately release urine to enhance sexual pleasure (This is a cultural practice!). Not recommended on scientific grounds

72. EFFECT OF SPERM MORPHOLOGY ANF MOTILITY ON FERTILITY When the number of physically abnormal sperms is more than 50% infertility is a likely result Abnormal heads, having two heads, abnormal tails The sperm may be structurally normal but may be nonmotile or relatively nonmotile . Infertility is likely to occur

73. ONLY ONE SPERM ENTERS THE OOCYTE When one sperm penetrates the zona pellucida of the ovum, calcium ions diffuse inward through the oocyte membrane and cause multiple cortical granules to be released by exocytosis from the oocyte into the perivitelline space. The granules contain substances that permeate all portions of the zona pellucida and prevent binding of additional sperm and they even cause any sperm that have already begun to bind to fall off.

74. OVARIAN CYCLE

75. OVULATION

76. OVULATION

77. FERTILIZATION Chemoatraction of the sperms to the ovum by substances produced by ovum Penetration of the sperm through the ovum coverings – release of enzyme hyaluronidase and other proteolytic enzymes present in the acrosome of the sperm The binding of the sperm to zona pellucida glycoprotein (ZP3) riggers acrosome reaction Fertilin : is a protein present in the acrosomal reacted sperm wich interacts with he protein present on the vitelline membrane and within 30 minutes the membranes of the sperm and ovum fuse , the genetic material of the sperm enters into the oocyte

78. 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

79. OVUM ACTIVATION

80. 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 implanation hCG enables continual of corpus luteum , and production of estrogen and progesterone

81. FERTLZATION

82. 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 zona pellucida and block entry of more sperms Occasionally more than one sperm are able to penetrate into the oocyte - non-identical twins or ???

83. FERTILISATION 1

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

85. TIME LINES From fertilization, the zygote, travels to the uterus Takes 3 t0 5 days to complete journey

86. 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

87. FIRST TRIMESTER Sustained by hormonal production from corpus luteum

88. SECOND AND THIRD TRIMESTER The placenta takes over the role of the corpus luteum And foetal adrenal gland

89. COMPONENTS OF PLACENTA

90. 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 Bohr effect

91. BOHR EFFECT

92. ROLE OF PLACENTA

93. HORMONAL INFLUENCES ON PREGNANCY

94. HORMONAL CHANGES DURING PRGNANCY

95. HORMONE LEVELS IN MATERNAL BLOOD DURING PREGNANCY

96. BLOOD VOLUME

97. HORMONAL CHNGES ACROSS PREGNANCY

98. PREGNANCY Carrying a baby in the womb from implantation to parturition 38 weeks Counting from menstruation: 40 weeks

99. 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

100. OXYTOCIN AND PARTURITION

101. LACTATION Estrogen and progesterone facilitate development of the breast Gradual increase of prolactin throughout pregnancy After parturition, estrogen and progesterone levels decrease abruptly, and lactation occurs. Stimulus for lctation : suckling

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

103. CONDOM

104. INTRAUTERINE DEVICE

105. WHEN THINGS GO WRONG Undescended testis ( cyrptorchidism ) 98.2% males testis in scrotum Sperm formation impaired at intrabdominal temperature Spermatogenesis at temperature 2 degrees below body temperature

106. 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

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

108. FETOPLACENTAL UNIT

109. INTERACTION BETWEEN PLACENTA AND FETAL ADRENAL

110. 5 β -REDUCTASE DEFICIENCY Individuals with this defect are pseudohermaphrodites They are born with male internal genitalia e g they have testes. BUT they have female external genitalia and are raised as girls When they reach puberty, the LH secretion is high and circulating testosterone levels are increased The individuals develop male body and male libido The clitoris enlarges Treatment is finasteride- a 5 β -reductase inhibitor

111. CRYPTORCHIDISM Undescended testes Occurs in 10% of newborn 2% at age 1 year 0.3% after puberty Early treatment is recommended High risk of cancer Infertililit y

112. PENILE ERECTION Erection occurs in s to physical and psychical stimuli