Reproductive System

1. Reproductive System Male Reproductive Physiology DR. ZAHOOR ALI DR. AMEL EASSAWI

2. Objectives • Describe the physiological functions of the major components of the male reproductive system. • Explain how the secretions of FSH and LH are regulated in the male and describe the actions of these hormones. • Describe spermatogenesis and the role of Sertoli cells, Leydigcells. • Explain the hormonal control of spermatogenesis and describe the effects of androgens on the male accessory sex organs. • Discuss the mechanisms of erection and ejaculation. • Discuss the various factors that affect male fertility.

3. MALE REPRODICTION SYSTEM

4. MALE REPRODUCTIVE System Primary Sex Organs: Testes Functional Compartments: • Seminiferous Tubules : Exocrine Function (spermatogenesis) • Interstitial Tissue: Endocrine Function: Leydigcells (interstitial cells). Androgen Secretion (mainly testosterone)

5. TESTICULAR MORPHOLOGY

6. MAJOR STEROIDS PRODUCED BY THE TESTIS

7. ANDROGEN PLASMA CONC. (ng/ml) PRODUCTION RATE (mg/day) TESTOSTERONE 700 7000 ANDROSTENEDIONE 100 2500 DIHYDROTESTERONE 30 300 TOTAL ANDROGEN PLASMA LEVELS AND PRODUCTION RATES IN MEN

8. TESTICULAR FUNCTION THROUGHOUT LIFETIME • The in utero 2nd trimester rise in testosterone (T) has been associated with sexual differentiation • The rise of T in the first year of life (peak at around 3 mos) is not understood (has been suggested to be associated with maturation of the sensitivity of the hypothalamic feedback system • The rise in T at the 11-17 year age is associated with pubery. • The decline in T in the old age group is associated with the aging process

9. Testosterone Testosterone • Steroid hormone. • Synthesized from the cholesterol precursor in the Leydig cells and also from the androstenedione secreted by the adrenal cortex. • Testosterone secretion rate is 4-9mg/dL in normal adults and very small amount is secreted in women.

10. TESTOSTERONE BASED ACTIVITIES

11. TESTOSTERONE BASED ACTIVITIES

12. TESTOSTERONE BASED ACTIVITIES

13. TESTOSTERONE BASED ACTIVITIES

14. TESTOSTERONE BASED ACTIVITIES Small amount produce by adrenal cortex A portion of the testosterone secreted by the testes is converted to estrogen outside the testes by the enzyme aromatase, which is widely distributed but most abundant in adipose tissue

15. TESTOSTERONE BASED ACTIVITIES Testosterone serves as a prohormone for some activities

16. Spermatogenesis • Complex process by which diploid primordial germ cells (spermatogonia) are converted into motile haploid spermatozoa (sperm). • Takes 64 days for development of mature sperm from spermatogonium (several hundred million sperm may reach maturity daily).

17. Spermatogenesis

18. Spermatogenesis Three major stages • Mitotic proliferation • Spermatogonia divide mitotically to give rise to two daughter cells • Sperm-forming daughter cell divides mitotically twice more to form four identical primary spermatocytes • Meiosis • Each primary spermatocyte forms two secondary spermatocytes yielding four spermatids after the second meiotic division • Theoretically, sixteen spermatozoa result from each spermatogonium that goes through process • Packaging • Production of motile spermatozoa from spermatids (Spermiogenesis).

19. Spermatogenesis 1. Complex process by which diploid primordial germ cells (spermatogonia) are converted into motile haploid spermatozoa (sperm). 2. It takes 64 days for development of mature sperm from spermatogonium (several hundred million sperm may reach maturity daily)

20. Spermatogenesis Spermatogenesis: Spermatids to Sperm

21. Spermatogenesis Spermatozoa: Consists of four parts • Head • Consists primarily of the nucleus (contains DNA) • Acrosome • containing hydrolytic enzymes that allow the sperm to penetrate and enter the egg • Midpiece • Area where mitochondria are concentrated • Tail • Provides mobility for spermatozoa

22. Functions of Sertoli cells • Form blood-testes barrier. • Provide nourishment and phagocytic function. • Secrete seminiferous tubule fluid which flushes released sperm from tubule into epididymis. • Secrete androgen-binding protein. • Site of action for testosterone & FSH to control spermatogenesis • Release inhibin, acts in negative-feedback fashion to regulate FSH secretion • Released mullerian inhibiting factor ( fetal development).

23. Control of Testicular Function

24. TESTICULAR CELL INTERACTIONS • Sertoli cell products estradiol, inhibin, activin and other proteins modulate leydig cell activity • Sertoli cell products modulate germ cell function • Leydig cell testosterone modulate peritubular & Sertoli cell function • Peritubular cell products influence Sertoli cell activity

25. REGULATION OF TESTICULAR FUNCTION • FSH and Testosterone are required for normal spermatogenesis. • LH is required for normal androgensynthesis. • 3. Sex steroids(mainly testosterone) feedback to suppress gonadotropin secretion at both the pituitary and hypothalamic levels. • 4. Feminizing Ledig cell tumors can suppress at hypothalamic and pituitary levels (excess estrogen production). • 5. Inhibin and Folistatin exert feedback suppression while Activin shows feedback stimulation of FSH secretion. • 6. During hyperprolactinonemia (elevated Prolactin) suppresses reproduction at the hypothalamic and pituitary levels (↓GnRH).

26. Semen • Milky white, sticky mixture of sperm and accessory gland secretions • Viscous alkaline fluid containing fructose, coagulating enzyme , and prostaglandins. • Provides a transport medium and nutrients (fructose), protects and activates sperm, and facilitates their movement. • Average volume is 2.5-3.5 ml per ejaculate. Normally 100 million sperm/ml of semen

27. Location and Functions of the Components of the Male Reproductive System

28. DISORDERS OF MALE SEXUAL FUNCTION A.Neonatal Life 1. Cryptorchidism descent of testes is incomplete, testes remain in the abdomen. 1. Bilateral: Impaired Testosterone secretion and spermatogenesis. 2. Unilateral :Normal Testosterone and impaired spermatogenesis. 2. 5Reductase Deficiency B. Puberty 1. True Precocious Puberty Premature activation of hypothalamic-pituitary axis. Early virilization and spermatogenesis.

29. DISORDERS OF MALE SEXUAL FUNCTION 2.Precocious Pesudo-Puberty Leydigcell tumors (a rare condition) leads to precocious pseudopuberty in prepubertal boys. Premature virilization without spermatogenesis. 3. Feminizing States 4. Delayed or Deficient Puberty 1. Isolated Gonadotropin deficiency(KALLMANN SYNDROME) 2. CNS disorders. 3. Testicular diseases.

30. DISORDERS OF MALE SEXUAL FUNCTION C. Adulthood 1. Infertility Under androgenization 1.Hypothalamic-Pituitary disorders Panhypopituitarism, Cushing disease, Hyper-prolactinemia. 2. Testicular disorders KlinefeltersSyndrome KAROYOTYPES: 47, XXY – CLASSIC FORM 46, XY – MOSAIC FORMS 48, XXYY, 48XXXY – VARIETY OF MOSAIC FORMS HIGHER FREQUENCY SYNDROMES

31. DISORDERS OF MALE SEXUAL FUNCTION 3. Acquired Defects 1. Viral Orchiditis 2. Trauma (Physical and Temperature) 3. Drugs (Alcohol, Marijuana) 4. Systemic diseases (Liver, Renal, Sickle Cell)

32. DISORDERS OF MALE SEXUAL FUNCTION 2. Infertility with Normal Virilization 1. Hypothalamic-Pituitary disorders 2. Testicular disorders *Varicocele, Immotile Cilia Syndrome, Germinal Cell Aplasia 3. Acquired defects 4. Systemic diseases 5. Impaired sperm Transport * HIGHER FREQUENCY SYNDROMES

33. DISORDERS OF MALE SEXUAL FUNCTION • Gynecomastia • Defined as presence of any palpable breast tissue in men. • Due to increase in estrogen-androgen ratio. • Three classes physiological, pathological and idiopathic. • Three time period(Birth, Puberty, Old Age). • Pysiological • The breast enlargement of newborns, the transient gynecomastia of adolescence and breast development of aging men, which cannot be associated with a pathological condition are considered to be physiological. • Pathological • Hypogonadism (Klinefelters). • Chronic liver diseases (cirrhosis, hepatitis). • Thyrotoxicosis. • Neoplasia. • Drugs (estrogen, testosterone)

34. DISORDERS OF MALE SEXUAL FUNCTION Erectile dysfunction or Impotence: Failure to achieve or maintain an erection suitable for sexual intercourse. Affect 50% of men between 40 and 70 years old. May be due to: 1. Psychological factors. 2. Physical factors. A. Nerve damage B. Medication that interfere with autonomic function C. Problem with blood flow to the penis. Sildenafil (Vigra): prescribed to treat erectile dysfunction. It does not produce an erection but it amplifies and prolongs an erectile response triggered by usual means of stimulation.

35. References • Human Physiology, Lauralee Sherwood, seventh edition. • Text book Physiology by Guyton &Hall,11th edition. • Text book of Physiology by Linda s. Contanzo, third edition. • Physiology by Berne and Levy, sixth edition.