1. Reproductive system physiology By Khorrami Ph.D. khorrami4@yahoo.com http://khorrami1962.spaces.live.com

4. Testis Seminiferous tubules 900*50cm …..450m 80% volume of testis Rete testis(anastomosing tubule) Efferent ductules Epididymis 5m long Head …immature sperm Body….sperm maturation Tail ….sperm maturation Vas deferens …. Decapacitation Ejaculatory duct

6. Spermatogenesis needs Sertoli Leydig Germ cells Myoepithelial cells Epithelial cells

7. Spermatogenesis Mitosis Miosis Spermiogenesis spermiation

8. Spermatogenesis Stem cells Mitosis Spermatogonia First spermatocyte First miosis Second spermatocyte Second miosis Spermatid sperm

10. Spermatogenesis Spermatogenesis: The production of spermatozoa in the sertoli cells Spermiogenesis: Conversion of the spermatids into spermatozoa Spermiation: Release of the spermatazoon into the lumen Capacitation: Final maturation of the spermatazoon in the female genital tract

11. 11 SPERMATOGENESIS SPERMATOGONIA (DIPLOID) MITOSIS PRIMARY SPERMATOCYTES (DIPLOID)

12. 12 SPERMATOGENESIS PRIMARY SPERMATOCYTES MEIOSIS I SECONDARY SPERMATOCYTES (HAPLOID) MEIOSIS II SPERMATIDS (HAPLOID) SPERMIOGENESIS SPERMATOZOA (HAPLOID)

14. 14 FROM SPERMATID TO SPERM

15. 15

16. 16 SERTOLI CELL

17. Spermatogenesis Inhibited by: Toxiphole Hypokalemia

21. Functions of Sertoli cells Blood-testis barrier(sertoli-cell barrier) by tight junction Adluminal compartment Basal compartment Supportive effects on germ cells Nutritive effects on germ cells Secretions

24. Secrete paracrine agents: FACILITATING LEYDIG CELL FUNCTION.

25. PHAGOCYTOSIS of defective sperm

27. Functions of leydig cells Steroidogenesis …8-18th week of gest. LH receptor/PRL(potentiate LH function) Testosteron ..5-7mg/day Androstenedione Relaxin-like factor A good marker for fully differentiated adult-type Leydig cells Weakly expressed in prepubertal Immature Leydig cells By insulin-like factor 3 gene

28. Relaxin-like factor 3(RLF) In estrogen-induced cryptorchidism, RLF levels in the testis are significantly reduced RLF secreted by theca cells of small antral follicles RLF secreted by the corpus luteum of the cycle and pregnancy

29. Testicular steroidogenesis

30. 28 MALE REPRODUCTION: HORMONAL REGULATION HYPOTHALAMUS - ve feedback GONADOTROPIN RELEASING HORMONE ANTERIOR PITUITARY - ve feedback FSH LH TESTES S E R T O L I CELL LEYDIG CELL TESTOSTERONE REP.TRACT & OTHER ORGANS SPERMATOGENESIS INHIBIN

31. 29 SEMEN ANALYSIS A test for infertility Semen contain: Sperms Secretions: Seminal vesicles Prostate Cowper’s glands Bulbo-urethral glands

32. 30 SEMEN ANALYSIS Volume: 2.5 to 3.5 ml/ejaculate Sperm count: 100 M/ml. <20% abnormal. <20 M/ml, sterile Sperm speed: 3mm/min. Reach fallopian tube 30- 40 min after coitus.

33. 31 SEMEN: COMPOSITION Color: white, opalescent Specific gravity: 1.028 Ph : 7.35 – 7.50

34. 32 SEMEN Liquid when ejaculated Coagulates: In vitro In vagina Undergoes secondary liquefaction after 15 min.

35. 33 SPERMATOZOA Fertile up to 24 to 48 hrs after deposition. Motile, for 48 – 60 hrs.`

36. Semen production Seminal vesicle (60%) Prostate (30%) Bulbouretral gland (cowper) Seminiferous tubule

37. Semen composition Fructose (for anaerobic metabolism of sperm)….sem.ves Glucose, A.A. and sorbitol (for aerobic metabolism of sperm) ….sem.ves Hormones (androgens, estrogens, progesterone) Decapacitation factors (cholesterol/esterol) ….sem.ves Prostoglandins ….sem.ves Citrate Ascorbic acid ….sem.ves Lecithin ….sem.ves Phosphorylcholine ….sem.ves Potassium Acid phosphatase Phosphate HCO3- Acrosin inhibitor Spermine (odor- coagulation) .....prostate Sperm coating proteins.....prostate Fibrinolysin .....prostate Zinc .....prostate

43. Testosterone & other steroids in man Testis 95% Adrenal 5% Total: 5-7mg/day DHT 50-100µg/day 17α-OH-progesterone 1-2mg/day Estradiol 10-15µg/day

44. Testosterone & other steroids Castration ->increase in LH & FSH Castration+ androgen ->increase in FSH only Role of inhibin

45. Androgen in plasma SHBG 40% Albumin 47% Other proteins

46. Metabolism of androgens By urine Excreted as 17KS 50% Gluco & sulphoconjugation in liver ↓ Urinary 17-KS Testis 30% Adrenal 70%

51. 49 FUNCTION OF PENIS IN COITUS (SEXUAL INTERCOURSE) Erection Ejaculation

52. 50 ERECTION VASCULAR: SMALL ARTERIAL DILATATION VENOCONSTRICTION PARASYMPATHETIC FACILITATION SYMPATHETIC INHIBITION SMOOTH MUSCLES RELAX

53. 51 PENILE ERECTION: REFLEX PATHWAYS INPUT FROM MECHANORECEPTORS OF PENIS THOUGHTS EMOTIONS SIGHT, SMELL NEURONS TO PENIS NEURONS RELEASE nonCholinergic NEUROTRANSMITTER (NO) INHIBITION ON SYMPATHETIC NEURONS PENIS ARTERIAL DILATATION + VENOCOMPRESSION = ERECTION

54. 52 EJACULATION Sympathetic facilitation Skeletal muscles contract Two events: EMISSION: Smooth muscles contract & semen sent into urethra EXPULSION: Rapid contraction of urethral smooth muscles.

55. 53 MALE REPRODUCTIVE ABNORMALITIES CRYPTORCHIDISM (UNDESCENDED TESTES) THE DESCENT OF TESTES IS INCOMPLETE IN 10% OF NEONATES SPONTANEOUS DESCENT OCCURS LATER INCIDENCE: 2% AT INFANCY & 0.3% AFTER PUBERTY COMPLICATIONS: INCREASED INCIDENCE OF TESTICULAR MALIGNANCIES & INFERTILITY.

58. Testosterone /effects

59. Synthesis of the male sex hormones in Leydig cells of the testis. P450SSC, 3b-DH, and P450c17 are the same enzymes as those needed for adrenal steroid hormone synthesis. 17,20-desmolase is the same as 17,20-lyase of adrenal hormone synthesis..

67. LH & FSH during life of a woman

68. HL: FSH>LH

69. Follicles At 20th week …..20mil At birth …………1-2 mil At puberty ……..300-400k During reproductive period..400-500

70. Uterine cycle Proliferative Secretory Ischemic Bleeding

71. Estrogen in proliferation phase Cell proliferation in endometrium Growth of ER & mitochondria in endometrium Increase glycogen storage Endometrial glands Dilation of arteries and coiled Increase in progesterone receptors Increase sensitivity & contractility of myometrium

73. Secretory phase Secretion of mucus Continue to proliferation Edema of endometrium Decrease contraction of myometrium

75. Menstrual cycle

76. Ovarian cycle Follicular phase Preovulatory phase Ovulatory phase Luteal phase Luteolysis phase

77. Steroidogenesis in ovary

78. Follicle graaf Theca interna is rich in Scc450(desmolase) Theca interna cells have LH receptors Granulosa cells are rich in aromatase Granulosa cells have LH & FSH receptors

80. Synthesis of the major female sex hormones in the ovary. Synthesis of testosterone and androstenedione from cholesterol occurs by the same pathways as indicated for synthesis of the male sex hormones.

83. Hohlweg effect Critical plasma concentration for estrogen 200pg/ml For 36 hrs No response to 100pg/ml Increase GnRH receptor on gonadotrops (est & PGE2) Increase the enzymatic activity of gonadotrops(est) Increase amplitude & frequency of GnRH(est & PGE2)

86. PGs & follicular rupture

87. Ovulation Androgen to estrogen microenvironment More FSH receptors Hohlweg effect Less OMI concentration Plasminogen activator Plasmin Fibrinolysin Collagenase Inhibin FSH & LH…..increase in cAMP Prostaglandin F2α( 2-5 hrs before ovulation) Completion of first miosis Contraction of ovarian smooth muscles Oxytocin

88. Ovulation

89. Luteal phase Progesterone secretion Negative Fern test LH support Maximum activity: 6-8 days after ovulation

90. Luteolysis PGF2α: Reduction in blood flow of corpus luteum Increase estrogen secretion Reduce response of corpus luteum to LH Increase OT secretion from CL

91. Menstrual cycle

94. Capacitation Remove of HMW glycoprotein (polylactoseamine) & peptides Whiplash-like pattern of hyperactivation of sperm Removing sterol & cholesterol from the surface Rearrangement of surface molecules Increase permeability to calcium Hyaloronidase activity Galactosyl-transferase activity

96. Acrosome reaction Calcium entrance- Ca-cal Increase cAMP Activation of phospholipaseA2 Increasing lysophospholipids Adhesion pH: 5.2 to 7:00 Segmentation of acrosome

100. Syngamy After enter the sperm, 2nd polar body After 30 min, disperse of sperm nucleus After 6-8 hrs, pronucleus & syngamy After 27-43 hrs, first division

105. Origin of testosterone in women

106. Factors affecting SHBG Stimulator Estrogen Hyperthyroidism Ageing Inhibitors Progestins (except OH-prog) GH Glucocorticosteroids Hypothyroidism

107. Relation of MCR of steroids & affinity to SHBG

108. DHEA-S concentration versus age

109. Distribution of plasma testosterone & estadiol

110. Aromatase activity in Muscle (25-30% in normal conditions) Adipose tissue Skin fibroblasts Hair follicles Brain Aromatase has more affinity to androstenedione than testosterone

111. Sources of estrone in women

112. Strogens Estradiol; 95% by ovary Estrone; peripheral conversion In normal women: E1/E2 <1