Advanced Reproduction Physiology (Lecture 1)

1. Advanced Reproduction Physiology(Lecture 1) Prepared by: A. Riasi http://riasi.iut.ac.ir Isfahan University of Technology College of Agriculture, Department of Animal Science

2. The syllabuses Puberty and sexual maturity Physiology of gamete production Hormonal & non-hormonal secretions of reproductive in male and female animals Physiology of pregnancy and embryo development

3. The syllabuses Physiology of parturition Pheromones Abnormality of reproduction Reproductive immunology Recent advance associated with reproductive physiology

4. References Reproductive in Farm Animals, By: E.S.E. Hafez Reproduction in Dairy Cattle 1&2, By: Gietema Improving the Reproductive Management of Dairy Cattle Subjected to Artificial Insemination, By: IAEA-TECDOC-1533 Review and Original Papers

5. Puberty and sexual maturity • Puberty is originated from Latin word “pubscere” • Hypothalamus control puberty in animals • Two centers in hypothalamus: • Tonic center • Surge center

6. Puberty Surge Surge Tonic Tonic

7. Puberty • In near to puberty age: • Sensitivity of the hypothalamic tonic center • GnRH and gonadotrophins secretion • Sensitivity of GnRH surge center in hypothalamus

8. Puberty

9. Puberty

10. Effect of testosterone on male brain T Testis T E2 Blood Brain Barrier Surge Center Does not Develop

11. Effect of estrogen on female brain aFP + E2 E2 Placenta E2 E2 E2 Ovary Blood Brain Barrier Surge Center Develops

12. Factors affecting puberty • Puberty may affected by different factors: • Heritability • Environmental factors • Birth month • Social condition • Nutritional factors • Age and weight

13. Role of leptin in puberty • Effect of a minimum percentage of body fat • Serum leptin concentrations • Leptin does not serve as triggering signal but acts mainly as a permissive signal that permits puberty to occur.

14. Role of leptin on puberty

15. Physiology of Testicular Function

16. The testes have two compartments: Tubular compartment (tubuli seminiferi) Interstitial compartment (interstitum) Functional organization of testis

17. The interstitial compartment: The leydig cells Secretion of testicular testosterone Secretion of insulin like factor 3 (INSL3) Immune cells Blood and lymph vessels Nerves Fibroblasts Loose connective tissue Functional organization of testis

18. Functional organization of testis • Different type of leydig cells (Ge and Hardy, 2007): • Stem Leydig cells as founder cell • Progenitor Leydig cells as a committed stem cell • Fetal Leydig cells as a terminally differentiated cell in the fetus • Adult Leydig cells as the terminally differentiated Leydig cell

19. The interstitial compartment also contains cells belonging to the immune system: Macrophages, probably influence the function of leydig cells: Proliferation Differentiation Steroid production Lymphocytes Functional organization of testis

20. Functional organization of testis Immunological compartments of the testis.Sertoli cells (S) traverse the testicular tubules, keeping in close contact with the germ cells. Together with the peritubular cells, they form the seminiferous epithelium. The blood–testis barrier (tight junctions) is built by tight junctions between neighboring S, dividing the seminiferous tubules into a basal and adluminal compartment. The interstitial space contains the Leydig cells (L) and the immune cells such as macrophages (MP), dendritic cells (D), mast cells (M), and T cells as well as blood vessels (BV) with migrating leukocytes

21. Spermatogenesis takes place in the tubular compartment: Germ cells Somatic cells The peritubular cells Sertoli cells Functional organization of testis

22. Peritubular cells produce several factors that are involved in cellular contractility (Holstein et al. 1996): Panactin Desmin Gelsolin Smooth muscle myosin and actin Functional organization of testis

23. Several regulators of cell contractions are reported: Oxytocin Oxytocin-like substances Prostaglandins Androgenic steroids Endothelins Endothelin converting enzymes Endothelin receptors Functional organization of testis

24. These cells also secrete extracellular matrix and factors typically expressed by connective tissue cells: Collagen Laminin Vimentin Fibronectin Growth factors Fibroblast Functional organization of testis

25. Sertoli cells synthesize and secrete a large variety of factors: Proteins Cytokines Growth factors Opioids Steroids Prostaglandins Modulators of cell division Functional organization of testis

26. The Cytoplasm of sertoli cells contains: Eendoplasmic reticulum Smooth type Rough type A Prominent Golgi apparatus Lysosomal granules Microtubuli and intermediate filaments Functional organization of testis

27. Another important functions of Sertoli cells: Final testicular volume Sperm production Functional organization of testis

28. Hormonal control of testicular function

29. Hormonal control of testicular function • Pituitary gonadotropes are the central structure controlling gonadal function. • In turn, are regulated by the hypothalamic gonadotropin-releasing hormone (GnRH). • GnRH secretion depends on the activation of the GPR54 receptor.

30. GnRH receptors are located on the surface of the GnRH neurons and stimulated by the peptide kisspeptin. The pituitary function is also under the control of gonadal steroids and peptides that influence its activity both directly and through the hypothalamus. Hormonal control of testicular function

31. The Gonadotropin-producing cells constitute approximately 15% of the adenohypophyseal cell. The same cell type is believed to secrete both gonadotropins. Pituitary gonadotropes are often found in close connection with prolactin cells. Hormonal control of testicular function

32. Dramatic changes by pubertal activation: The proximity of several stimulated endocrine cells types to each other and to the germinal cell line. Central feedback actions: FSH LH Testosterone Hormonal control of testicular function

33. In male testosterone is major the hormone controlling GnRH secretion Testosterone can act as such or after metabolism to DHT or estradiol. Hormonal control of testicular function

34. During spermatogenesis gonadotropes regulate testicular function. Testosterone and FSH affect the seminiferous tubules and enhance spermatogenesis LH affect the release of sperm from germinal epithelium (spermiation) Hormonal control of spermatogenesis

35. High concentration of testosterone may find in seminiferous tubules, rete testis, afferent tubules and epydidymis. Effect of inhibin and activin on FSH secretion and spermatogenesis Hormonal control of testicular function

36. The other hormones may affect testicular funtion: Prolactin GH and IGF-I Insulin Glucocorticoids Thyroid hormones PGE2 Testicular GnRH Hormonal control of testicular function

37. Androgens are essential for: The development and function of testes Maturation of secondary sexual characteristics Masculinization of the bone-muscle apparatus Libido Stimulation of spermatogenesis Testicular androgens

38. Physiological effects of androgens depend on different factors: Number of androgen molecules Distribution of androgens and their metabolites inside the cell Interaction with the receptors Polyglutamine number of the amino acid sequence in the androgen receptor Receptor activation Testicular androgens

39. In turn, androgen concentrations in the blood depend on: The synthesis rate Balanced by metabolic conversion and excretion. Testicular androgens

40. The main site of androgen production in the testis is the Leydig cell. Since Leydig cells cannot store androgens, de novo biosynthesis takes place continuously. LH as the central regulatory factor controls both steroidogenesis and Leydig cell cholesterol homeostasis in vivo. Testicular androgens

41. Testicular androgens

42. Cholesterol is stored in cytoplasmic lipid droplets. The number of lipid droplets is inversely related to the rate of androgen synthesis in the Leydig cell. Testicular androgens

43. Testosterone moves from the leydig cells into: Blood vessel Lymphatic vessel Seminiferous tubules Testicular androgens

44. Testosterone also give rise to two other potent androgens: Dihydrotestosterone (DHT) 5α-androstandiol Testicular androgens

45. Testicular androgens

46. Circulating testosterone is found in three forms Free Bounded with a liver-drived sex steroid-binding globulin (SSBG) Bounded with albumin and other proteins Testicular androgens

47. Testosterone is excreted by urine: As glucronide (1% of daily production of testosterone) 17-ketosteroids products Testicular androgens

48. Testicular androgens Testosterone (T) is synthesized in the testis. After entering the target cells (in the hypothalamus, pituitary, testis and wolffian duct) T is directly bound to the androgen receptor (AR) and the complex T-AR binds to specific DNA sequences and regulates gene transcription, which can result different works.

49. Testicular androgens Specific actions of Dihydrotestosterone (DHT). After entering the T to target cells (in the urogenital sinus, urogenital tubercle, and several additional androgen target tissues) T is metablized to 5α-Dihydrotestosterone (DHT) by the enzyme 5α-Reductase type 2. DHT binds directly to the androgen receptor (AR) and the complex DHT-AR interacts to specific DNA sequences and regulates gene transcription, which can result in differentiation and development of the prostate, the external genitalia and at puberty in several secondary male characteristics.

50. Testicular androgens