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)

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• 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.

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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