W2L1 Mon Testicular endocrinology and Spermatogenesis Flashcards
What is spermatogenesis, what does it need and where does it occur
process from spermatogonium to spermatozoa (65-75 days)
§ Requires the action of FSH, ABP + testosterone on Sertoli + germ cells
§ Takes place in intercellular (adluminal) space aided by Sertoli cell
What is Spermiogenesis
part of spermatogenesis, process of cytodifferentiation of round spermatid to elongated sperm (spermatozoa)
What is Spermiation
sperm release into the lumen
Cellular basis of spermatogenesis
The process takes place from the basal to adluminal side of sterotoli cell, Cellular basis of spermatogenesis is sub-divided into:
* Mitotic proliferation
* Meiotic divisions
* nuclear meiosis (karyokinesis)
* cellular meiosis (cytokinesis)
* Cytodifferentiation
Process of spermatogenesis: Mitotic Proliferation
§ Spermatogonia (progenitor stem cells) rest close to basement membrane of seminiferous tubules
§ 4 mitotic divisions (~42 hour intervals) producing spermatogonial daughter cells type A1-A4
§ Spermatogonium type A1-4 → intermediate spermatogonium → spermatogonium type B
§ Type B differentiates into resting primary spermatocyte (large nucleus) which migrates through blood testis barrier into adluminal space
Process of spermatogenesis: Cellular meiotic divisions
§ 1st meiotic division (several steps): resting primary spermatocyte (2n) → secondary spermatocyte (n)
§ 2nd meiotic division: secondary spermatocyte (n) → round spermatid (n)
Ø Round spermatids: smaller size, large nucleus + non-motile
Ø Nuclear divisions (karyokinesis) is complete, cytoplasmic divisions (cytokinesis) of round spermatids not completed until full spermatozoa formation
Process of spermatogenesis: Karyotype meiotic divisions
- Separation of the chromatids then duplication of DNA contents of the resting primary spermatocytes – two identical chromatids with two centromeres – tetrads (1) (2n but not 4n)
- First meiotic division:
- synaptonemal contact – one centromere
- crossing over – genetic exchange (diversification) (2)
- separation of homologous chromosomes – 1/2 number of chromatids but double amount of DNA (duplication) (n) (3)
- secondary spermatocytes (arrow)
- Second meiotic division:
- separation of individual chromatids –
- 1/2 number (not 1/4) of identical chromatids and normal amount of DNA (n) (4)
- round spermatids (haploid – n)
Cytodifferentiation / Spermiogenesis
Differentiation of round spermatids into elongated spermatozoa
* Cytoplasmic remodelling and shape changing from round to elongated
* formation of acrosome
* formation of the tail from centrioles
* migration of cytoplasmic contents as mitochondria toward the back
* condensation of RNAs – head formation
* removal of excess cytoplasm including the connection elements by Sertoli cell phagocytosis
* spermiation: release of spermatozoa into the lumen of seminiferous tubules
Sertoli cells and Spermatogenesis
Spermatogenesis takes place in the intercellular (adluminal) space aided by Sertoli cell (sustentacular cell)
* Sertoli cells support, protect and nourish germ cells & allow intercellular communication
* Produce hormones and peptides; oestrogen, inhibin, activin
* Blood-testis barrier
Duration of spermatogenesis in different species
- Duration of the spermatogenic cycle is constant and characteristic of each species
- Different regions along the seminiferous tubule are undergoing different stages of the spermatogenic cycle- spatial differs (spermatogenic wave)
Sperm Morphology
- Sperm: highly specialised b/w species with same basic parts (lifespan 48-72 hours in female tract)
- Made to reach and penetrate oocyte (5μm wide and 55–65μm long)
§ Head: nucleus, DNA + acrosome (fluid-filled sac w/ proteolytic enzyme that break down cells coating egg)
§ Midpiece: centriole anchors mitochondria (generates energy ATP)
§ Tail: flagellum for locomotion (microtubules that move alongside each other to cause wave motion)
Testicular endocrinology during foetal and neonatal periods
§ Placenta/early embryo produces chorionic gonadotrophin (hCG, eCG)
Ø Foetal Leydig cells bind hCG to facilitate production of testosterone
§ Testosterone acts on + drives formation of testis, duct system, external genitalia + accessory organs
Ø Drives development of hypothalamus inducing GnRH release
Ø GnRH-induced LH stimulates foetal Leydig cell development = androgens
§ Androgen levels drop at birth (placenta removed) then increase during neonatal period
Ø Foetal Leydig cells degenerate during juvenile period = ↓androgen levels
Testicular Endocrinology after puberty
§ GnRH produced by hypothalamus into anterior pituitary gland to stimulate production of FSH + LH
Ø FSH + LH transfer through systemic circulation to testes
§ LH bind to Leydig cells to facilitate conversion of cholesterol → testosterone (steroidogenesis)
Ø Testosterone passes basement membrane into Sertoli cells
§ FSH bind to Sertoli cell basement membrane to facilitate conversion of Testosterones → Oestrogen
Ø Oestrogen required for healthy sperm production + regulating fluid in testes
§ ABP maintain steroids in local environment to facilitate spermatogonia → spermatids
§ Testosterone (Leydig): negative feedback to hypothalamus/pituitary to inhibit GnRH
§ Inhibin (Sertoli): negative feedback to pituitary to inhibit FSH
§ Hypophysectomy: removal of pituitary gland to stop steroidogenesis + spermatogenesis
Steroidogenesis Two-Cell Theory: leydig cell
Leydig cells:
§ Post-puberty: ↑LH levels = fibroblast-like interstitial cells differentiate into Leydig cells
§ Lipid droplets containing cholesterol taken up (steroid precursor)
§ Mitochondria: site of conversion of cholesterol → pregnenolone via P450SCC (rate limiting)
§ Smooth endoplasmic reticulum: site of production of all other steroid hormones
§ Leydig cells stimulated by LH to produce androgen
Ø Most androgens diffuse through cell membrane + interstitial space into blood
Ø Some androgens pass through basement membrane to Sertoli cells
Steroidogenesis Two-Cell Theory: Sertoli Cells
§ Post-puberty: ↑FSH levels = Sertoli cell proliferation + differentiation
§ FSH acts via cAMP + Ca2+ = secretion of ABP, inhibin, transferrin, aromatase, lactate
§ Androgens from Leydig cells → DHT by 5a-reductase OR → oestrogens by aromatase
§ Oestrogens aid in spermatogenesis + fluid reabsorption in testis + epididymis
§ Testosterone/DHT binds to ABP to promote spermatogenesis or is excreted into lumen of seminiferous tubules (mature sperm along tract)
