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Reproductive system physiology
ByKhorrami Ph.D.
khorrami4@yahoo.com http://khorrami1962.spaces.live.com
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
Spermatogenesis needs
• Sertoli• Leydig• Germ cells• Myoepithelial cells• Epithelial cells
Spermatogenesis
• Mitosis • Miosis• Spermiogenesis• spermiation
Spermatogenesis • Stem cells• Mitosis• Spermatogonia• First spermatocyte• First miosis• Second spermatocyte• Second miosis• Spermatid• sperm
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
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SPERMATOGENESIS
SPERMATOGONIA (DIPLOID)
PRIMARY SPERMATOCYTE
S(DIPLOID)
MITOSIS
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SPERMATOGENESIS PRIMARY SPERMATOCYTES
SECONDARY SPERMATOCYTES(HAPLOID)
MEIOSIS I
SPERMATIDS (HAPLOID)
SPERMATOZOA (HAPLOID)
MEIOSIS II
SPERMIOGENESIS
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FROM SPERMATID TO SPERM
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16SERTOLI CELL
Spermatogenesis
• Inhibited by:• Toxiphole• Hypokalemia
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
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FUNCTIONS OF SERTOLI CELLS
• Secrete ANDROGEN BINDING PROTEIN & LUMINAL FLUID.
• Secrete PARACRINE AGENTS Stimulating proliferation & differentiation.
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• Secrete the regulatory protein INHIBIN.• Secrete paracrine agents: FACILITATING
LEYDIG CELL FUNCTION.• PHAGOCYTOSIS of defective sperm• Secrete MULLERIAN INHIBITING
HORMONE(MIH)
FUNCTIONS OF SERTOLI CELLS
Secretions of Sertoli cells• Mullerian inhibitory factor (MIF)• Aromatase • Androgen binding protein (ABP)• Inhibin • Estrone/estradiol • DHT• GnRH-like peptide• Ceruloplasmin• Plasminogen activator• Follistatin • IGF-1• TGF• Transferrin• Cytokines
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
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
Testicular steroidogenesis
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MALE REPRODUCTION: HORMONAL REGULATIONHYPOTHALAMUS
GONADOTROPIN RELEASING HORMONE
ANTERIOR PITUITARY
TESTESFSH LH
SERTOLICELL
LEYDIG CELL
TESTOSTERONE
INHIBIN
REP.TRACT& OTHER ORGANSSPERMATOGENESIS
- ve feedback
- ve
fee
dbac
k
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SEMEN ANALYSIS
• A test for infertility• Semen contain:
– Sperms– Secretions:
• Seminal vesicles• Prostate• Cowper’s glands• Bulbo-urethral glands
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• 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.
SEMEN ANALYSIS
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SEMEN: COMPOSITION
• Color: white, opalescent• Specific gravity: 1.028• Ph : 7.35 – 7.50
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SEMEN• Liquid when ejaculated• Coagulates:
– In vitro– In vagina
• Undergoes secondary liquefaction after 15 min.
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SPERMATOZOA
• Fertile up to 24 to 48 hrs after deposition.• Motile, for 48 – 60 hrs.`
Semen production
• Seminal vesicle (60%)• Prostate (30%)• Bulbouretral gland (cowper)• Seminiferous tubule
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• Phosphoryl choline ….sem.ves• Potassium• Acid phosphatase• Phosphate• HCO3-
• Acrosin inhibitor• Spermine (odor- coagulation) .....prostate• Sperm coating proteins.....prostate• Fibrinolysin .....prostate• Zinc .....prostate
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
Testosterone & other steroids
• Castration →increase in LH & FSH• Castration+ androgen →increase in FSH only• Role of inhibin
Androgen in plasma
• SHBG 40%• Albumin 47%• Other proteins
Metabolism of androgens
• By urine• Excreted as 17KS 50%• Gluco & sulphoconjugation in liver• ↓• Urinary 17-KS
– Testis 30%– Adrenal 70%
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• Erection• Ejaculation
FUNCTION OF PENIS IN COITUS (SEXUAL INTERCOURSE)
50
• VASCULAR:– SMALL ARTERIAL DILATATION– VENOCONSTRICTION
• PARASYMPATHETIC FACILITATION • SYMPATHETIC INHIBITION
– SMOOTH MUSCLES RELAX
ERECTION
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PENILE ERECTION: REFLEX PATHWAYS
THOUGHTSEMOTIONS
SIGHT, SMELL
INPUT FROM MECHANORECEPTORS
OF PENIS
NEURONS TO PENISNEURONS RELEASE nonCholinergic NEUROTRANSMITTER (NO)
INHIBITION ON SYMPATHETIC NEURONS
PENISARTERIAL DILATATION + VENOCOMPRESSION
= ERECTION
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EJACULATION• Sympathetic facilitation • Skeletal muscles contract• Two events:
1. EMISSION: Smooth muscles contract & semen sent into urethra
2. EXPULSION: Rapid contraction of urethral smooth muscles.
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.
Testosterone /effects
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..
LH & FSH during life of a woman
HL: FSH>LH
Follicles
• At 20th week …..20mil• At birth …………1-2 mil• At puberty ……..300-400k• During reproductive period..400-500
Uterine cycle
• Proliferative• Secretory • Ischemic• Bleeding
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
Secretory phase
• Secretion of mucus• Continue to proliferation• Edema of endometrium• Decrease contraction of myometrium
Menstrual cycle
Ovarian cycle
• Follicular phase• Preovulatory phase• Ovulatory phase• Luteal phase • Luteolysis phase
Steroidogenesis in ovary
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
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.
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)
PGs & follicular rupture
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
Ovulation
Luteal phase
• Progesterone secretion• Negative Fern test• LH support• Maximum activity: 6-8 days after ovulation
Luteolysis
• PGF2α:– Reduction in blood flow of corpus luteum– Increase estrogen secretion– Reduce response of corpus luteum to LH– Increase OT secretion from CL
Menstrual cycle
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
Acrosome reaction
• Calcium entrance- Ca-cal• Increase cAMP• Activation of phospholipaseA2• Increasing lysophospholipids• Adhesion • pH: 5.2 to 7:00• Segmentation of acrosome
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
Origin of testosterone in women
Factors affecting SHBG
Stimulator • Estrogen• Hyperthyroidism• Ageing
Inhibitors • Progestins (except OH-
prog)• GH• Glucocorticosteroids • Hypothyroidism
Relation of MCR of steroids & affinity to SHBG
DHEA-S concentration versus age
Distribution of plasma testosterone & estadiol
Aromatase activity in
• Muscle (25-30% in normal conditions)• Adipose tissue• Skin fibroblasts• Hair follicles• Brain
• Aromatase has more affinity to androstenedione than testosterone
Sources of estrone in women
Strogens
• Estradiol; 95% by ovary• Estrone; peripheral conversion• In normal women: E1/E2 <1
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