Reproductive system
    physiology

          By
    Khorrami Ph.D.


          khorrami4@yahoo.com
   http://khorrami1962...
Testis
• Seminiferous tubules
   – 900*50cm …..450m
   – 80% volume of testis
• Rete testis(anastomosing tubule)
• Efferen...
Spermatogenesis needs
•   Sertoli
•   Leydig
•   Germ cells
•   Myoepithelial cells
•   Epithelial cells
Spermatogenesis
•   Mitosis
•   Miosis
•   Spermiogenesis
•   spermiation
Spermatogenesis

• Spermatogenesis: The production of
  spermatozoa in the sertoli cells
• Spermiogenesis: Conversion of t...
Spermatogenesis
•   Stem cells
•   Mitosis
•   Spermatogonia
•   First spermatocyte
•   First miosis
•   Second spermatocy...
SPERMATOGENESIS

       SPERMATOGONIA (DIPLOID)



            MITOSIS



                PRIMARY
            SPERMATOCYTE...
SPERMATOGENESIS
             PRIMARY SPERMATOCYTES

            MEIOSIS I



            SECONDARY SPERMATOCYTES
         ...
FROM SPERMATID TO SPERM




           15
16
SERTOLI CELL
           17
Spermatogenesis
• Inhibited by:
• Toxiphole
• Hypokalemia
Functions of Sertoli cells
• Blood-testis barrier(sertoli-cell barrier) by
  tight junction
  – Adluminal compartment
  – ...
FUNCTIONS OF SERTOLI CELLS
•    Secrete ANDROGEN BINDING PROTEIN &
     LUMINAL FLUID.
•    Secrete PARACRINE AGENTS Stimu...
FUNCTIONS OF SERTOLI CELLS
• Secrete the regulatory protein INHIBIN.
• Secrete paracrine agents: FACILITATING
  LEYDIG CEL...
Secretions of Sertoli cells
•   Mullerian inhibitory factor (MIF)
•   Aromatase
•   Androgen binding protein (ABP)
•   Inh...
Functions of leydig cells
• Steroidogenesis …8-18th week of gest.
• LH receptor/PRL(potentiate LH function)
• Testosteron ...
Relaxin-like factor 3(RLF)
• In estrogen-induced cryptorchidism, RLF
  levels in the testis are significantly reduced
• RL...
Testicular steroidogenesis
MALE REPRODUCTION: HORMONAL REGULATION
                              HYPOTHALAMUS




                                    ...
SEMEN ANALYSIS
• A test for infertility
• Semen contain:
  – Sperms
  – Secretions:
     •   Seminal vesicles
     •   Pro...
SEMEN ANALYSIS
• Volume: 2.5 to 3.5 ml/ejaculate
• Sperm count: 100 M/ml.
• <20% abnormal.
• <20 M/ml, sterile
• Sperm spe...
SEMEN: COMPOSITION

• Color: white, opalescent
• Specific gravity: 1.028
• Ph : 7.35 – 7.50




                   32
SEMEN
• Liquid when ejaculated
• Coagulates:
  – In vitro
  – In vagina
• Undergoes secondary liquefaction after
  15 min....
SPERMATOZOA
• Fertile up to 24 to 48 hrs after deposition.
• Motile, for 48 – 60 hrs.`




                         34
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 m...
Testosterone & other steroids in
             man
•   Testis     95%
•   Adrenal    5%
•   Total:     5-7mg/day
•   DHT   ...
Testosterone & other steroids
• Castration →increase in LH & FSH
• Castration+ androgen →increase in FSH only
• Role of in...
Androgen in plasma
• SHBG         40%
• Albumin      47%
• Other proteins
Metabolism of androgens
•   By urine
•   Excreted as 17KS      50%
•   Gluco & sulphoconjugation in liver
•   ↓
•   Urinar...
FUNCTION OF PENIS IN COITUS
    (SEXUAL INTERCOURSE)

• Erection
• Ejaculation




                50
ERECTION
• VASCULAR:
  – SMALL ARTERIAL DILATATION
  – VENOCONSTRICTION
• PARASYMPATHETIC FACILITATION
• SYMPATHETIC INHIB...
PENILE ERECTION: REFLEX PATHWAYS
                                       INPUT FROM
   THOUGHTS                         MEC...
EJACULATION
•   Sympathetic facilitation
•   Skeletal muscles contract
•   Two events:
    1. EMISSION: Smooth muscles con...
MALE REPRODUCTIVE
    ABNORMALITIES
• CRYPTORCHIDISM (UNDESCENDED
  TESTES)
 – THE DESCENT OF TESTES IS INCOMPLETE IN
   1...
Testosterone /effects
Synthesis of the male sex hormones in Leydig
cells of the testis. P450SSC, 3b-DH, and
P450c17 are the same enzymes as thos...
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..4...
Uterine cycle
• Proliferative
• Secretory
• Ischemic
• Bleeding
Estrogen in proliferation phase
•   Cell proliferation in endometrium
•   Growth of ER & mitochondria in endometrium
•   I...
Secretory phase
• Secretion of mucus
• Continue to proliferation
• Edema of endometrium
• Decrease contraction of myometri...
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 ...
Synthesis of the major female sex hormones in the ovary. Synthesis of testosterone and
androstenedione from cholesterol oc...
Hohlweg effect
• Critical plasma concentration for estrogen
  – 200pg/ml
  – For 36 hrs
  – No response to 100pg/ml
• Incr...
PGs & follicular rupture
Ovulation
•   Androgen to estrogen microenvironment
•   More FSH receptors
•   Hohlweg effect
•   Less OMI concentration
•...
Ovulation
Luteal phase
•   Progesterone secretion
•   Negative Fern test
•   LH support
•   Maximum activity: 6-8 days after ovulati...
Luteolysis
• PGF2α:
  –   Reduction in blood flow of corpus luteum
  –   Increase estrogen secretion
  –   Reduce response...
Menstrual cycle
Capacitation
• Remove of HMW glycoprotein (polylactoseamine) &
  peptides
• Whiplash-like pattern of hyperactivation of sp...
Acrosome reaction
• Calcium entrance- Ca-cal
• Increase cAMP
• Activation of phospholipaseA2
• Increasing lysophospholipid...
Syngamy
•   After enter the sperm, 2nd polar body
•   After 30 min, disperse of sperm nucleus
•   After 6-8 hrs, pronucleu...
Origin of testosterone in women
Factors affecting SHBG

Stimulator          Inhibitors
• Estrogen          • Progestins (except OH-
• Hyperthyroidism     ...
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
...
Sources of estrone in women




         Aromatase
Strogens
• Estradiol; 95% by ovary
• Estrone; peripheral conversion
• In normal women: E2/E1 >1
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
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Reproductive Male Female
Reproductive Male Female
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Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
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Reproductive Male Female
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Reproductive Male Female
Reproductive Male Female
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Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
Reproductive Male Female
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Reproductive Male Female

  1. 1. Reproductive system physiology By Khorrami Ph.D. khorrami4@yahoo.com http://khorrami1962.spaces.live.com
  2. 2. 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
  3. 3. Spermatogenesis needs • Sertoli • Leydig • Germ cells • Myoepithelial cells • Epithelial cells
  4. 4. Spermatogenesis • Mitosis • Miosis • Spermiogenesis • spermiation
  5. 5. 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
  6. 6. Spermatogenesis • Stem cells • Mitosis • Spermatogonia • First spermatocyte • First miosis • Second spermatocyte • Second miosis • Spermatid • sperm
  7. 7. SPERMATOGENESIS SPERMATOGONIA (DIPLOID) MITOSIS PRIMARY SPERMATOCYTES (DIPLOID) 12
  8. 8. SPERMATOGENESIS PRIMARY SPERMATOCYTES MEIOSIS I SECONDARY SPERMATOCYTES (HAPLOID) MEIOSIS II SPERMATIDS (HAPLOID) SPERMIOGENESIS SPERMATOZOA (HAPLOID) 13
  9. 9. FROM SPERMATID TO SPERM 15
  10. 10. 16
  11. 11. SERTOLI CELL 17
  12. 12. Spermatogenesis • Inhibited by: • Toxiphole • Hypokalemia
  13. 13. 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
  14. 14. FUNCTIONS OF SERTOLI CELLS • Secrete ANDROGEN BINDING PROTEIN & LUMINAL FLUID. • Secrete PARACRINE AGENTS Stimulating proliferation & differentiation. 23
  15. 15. FUNCTIONS OF SERTOLI CELLS • Secrete the regulatory protein INHIBIN. • Secrete paracrine agents: FACILITATING LEYDIG CELL FUNCTION. • PHAGOCYTOSIS of defective sperm • Secrete MULLERIAN INHIBITING HORMONE(MIH) 24
  16. 16. 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
  17. 17. 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
  18. 18. 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
  19. 19. Testicular steroidogenesis
  20. 20. MALE REPRODUCTION: HORMONAL REGULATION HYPOTHALAMUS - ve feedback GONADOTROPIN RELEASING HORMONE ANTERIOR PITUITARY - ve feedback FSH LH TESTES S E LEYDIG CELL R T O TESTOSTERONE L I REP.TRACT CELL SPERMATOGENESIS & OTHER ORGANS INHIBIN 29
  21. 21. SEMEN ANALYSIS • A test for infertility • Semen contain: – Sperms – Secretions: • Seminal vesicles • Prostate • Cowper’s glands • Bulbo-urethral glands 30
  22. 22. 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. 31
  23. 23. SEMEN: COMPOSITION • Color: white, opalescent • Specific gravity: 1.028 • Ph : 7.35 – 7.50 32
  24. 24. SEMEN • Liquid when ejaculated • Coagulates: – In vitro – In vagina • Undergoes secondary liquefaction after 15 min. 33
  25. 25. SPERMATOZOA • Fertile up to 24 to 48 hrs after deposition. • Motile, for 48 – 60 hrs.` 34
  26. 26. Semen production • Seminal vesicle (60%) • Prostate (30%) • Bulbouretral gland (cowper) • Seminiferous tubule
  27. 27. 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
  28. 28. 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
  29. 29. Testosterone & other steroids • Castration →increase in LH & FSH • Castration+ androgen →increase in FSH only • Role of inhibin
  30. 30. Androgen in plasma • SHBG 40% • Albumin 47% • Other proteins
  31. 31. Metabolism of androgens • By urine • Excreted as 17KS 50% • Gluco & sulphoconjugation in liver • ↓ • Urinary 17-KS – Testis 30% – Adrenal 70%
  32. 32. FUNCTION OF PENIS IN COITUS (SEXUAL INTERCOURSE) • Erection • Ejaculation 50
  33. 33. ERECTION • VASCULAR: – SMALL ARTERIAL DILATATION – VENOCONSTRICTION • PARASYMPATHETIC FACILITATION • SYMPATHETIC INHIBITION – SMOOTH MUSCLES RELAX 51
  34. 34. PENILE ERECTION: REFLEX PATHWAYS INPUT FROM THOUGHTS MECHANORECEPTORS EMOTIONS OF PENIS SIGHT, SMELL NEURONS TO PENIS NEURONS RELEASE nonCholinergic NEUROTRANSMITTER (NO) INHIBITION ON SYMPATHETIC NEURONS PENIS ARTERIAL DILATATION + VENOCOMPRESSION = ERECTION 52
  35. 35. 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
  36. 36. 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. 54
  37. 37. Testosterone /effects
  38. 38. 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..
  39. 39. LH & FSH during life of a woman
  40. 40. HL: FSH>LH
  41. 41. Follicles • At 20th week …..20mil • At birth …………1-2 mil • At puberty ……..300-400k • During reproductive period..400-500
  42. 42. Uterine cycle • Proliferative • Secretory • Ischemic • Bleeding
  43. 43. 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
  44. 44. Secretory phase • Secretion of mucus • Continue to proliferation • Edema of endometrium • Decrease contraction of myometrium
  45. 45. Menstrual cycle
  46. 46. Ovarian cycle • Follicular phase • Preovulatory phase • Ovulatory phase • Luteal phase • Luteolysis phase
  47. 47. Steroidogenesis in ovary
  48. 48. 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
  49. 49. 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.
  50. 50. 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)
  51. 51. PGs & follicular rupture
  52. 52. 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
  53. 53. Ovulation
  54. 54. Luteal phase • Progesterone secretion • Negative Fern test • LH support • Maximum activity: 6-8 days after ovulation
  55. 55. Luteolysis • PGF2α: – Reduction in blood flow of corpus luteum – Increase estrogen secretion – Reduce response of corpus luteum to LH – Increase OT secretion from CL
  56. 56. Menstrual cycle
  57. 57. 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
  58. 58. Acrosome reaction • Calcium entrance- Ca-cal • Increase cAMP • Activation of phospholipaseA2 • Increasing lysophospholipids • Adhesion • pH: 5.2 to 7:00 • Segmentation of acrosome
  59. 59. 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
  60. 60. Origin of testosterone in women
  61. 61. Factors affecting SHBG Stimulator Inhibitors • Estrogen • Progestins (except OH- • Hyperthyroidism prog) • Ageing • GH • Glucocorticosteroids • Hypothyroidism
  62. 62. Relation of MCR of steroids & affinity to SHBG
  63. 63. DHEA-S concentration versus age
  64. 64. Distribution of plasma testosterone & estadiol
  65. 65. Aromatase activity in • Muscle (25-30% in normal conditions) • Adipose tissue • Skin fibroblasts • Hair follicles • Brain • Aromatase has more affinity to androstenedione than testosterone
  66. 66. Sources of estrone in women Aromatase
  67. 67. Strogens • Estradiol; 95% by ovary • Estrone; peripheral conversion • In normal women: E2/E1 >1

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