Lecture 2 - Physiology of the Male Reproductive System PDF

PP2201 Reproduction Lecture 2 Assoc. Prof. Damien Paris [email protected]  Spermatogenesis:  mitosis vs. meiosis  spermatogenesis  sex determination  endocrine regulation  Sperm structure & fertilization  Actions of testosterone  Background reading:  Marieb & Hoehn 2...

PP2201 Reproduction Lecture 2 Assoc. Prof. Damien Paris [email protected]  Spermatogenesis:  mitosis vs. meiosis  spermatogenesis  sex determination  endocrine regulation  Sperm structure & fertilization  Actions of testosterone  Background reading:  Marieb & Hoehn 2013 Human Anatomy & Physiology. 9th edition – Chapter 27 & 28 (fertilization) (via LearnJCU)  Describe the process of spermatogenesis  Understand the functional anatomy of spermatozoa & how it relates to the process of fertilization  Discuss the role of various hormones in the regulation of spermatogenesis  Appreciate the actions of testosterone on primary & secondary sex characteristics in the male  allows genetic mixing ≈ ↑ offspring fitness Gametogenesis (spermatogenesis) different reproductive anatomy allows for delivery of genes (via gametes) Development of Male Phenotype  formation of gametes (sex cells):  spermatogenesis → testes  oogenesis → ovaries  involves halving of the chromosomes via meiosis:  avoids polyploidy → detrimental diploid haploid adult (2n=46) ÷2= gametes (n=23) haploid haploid diploid sperm (n=23) + egg (n=23) = zygote (2n=46)  The formation of sperm occurs in the seminiferous tubules of the Marieb & Hoehn 2010 testes & takes ~64 to 72 days  Process involves both mitotic & meiotic cell divisions  Mitosis:  equal division to produce 2 identical daughter cells with same number of chromosomes (replenishes spermatogonial stem cell reserve)  Meiosis:  reducing division to produce 4 unique daughter cells with half the number of chromosomes (sperm for reproduction)  S phase DNA cross-over 2 divisions 1 division 4 unique 2 identical daughters daughters (haploid) (diploid)  1 cycle ≈70 days Spermatogonium (stem cell) Sertoli Type A daughter cell cell nucleus (remains at basal lamina as a stem cell) Basal lamina Mitosis Type B daughter cell Growth Meiosis I Tight junction (enters adluminal (between sustentacular cells) compartment) Primary spermatocyte Secondary spermatocytes Meiosis II Early spermatids Late spermatids Cytoplasmic bridge Spermatozoa Lumen of seminifer- ous tubule Marieb & Hoehn 2010  Cytoplasmic remodelling of the spermatid is called spermiogenesis  Packages chromosomes for delivery  Spermatids change from round to elongated cells with an acrosome “cap” containing enzymes & a flagellum  When fully differentiated, spermatozoa released into lumen of seminiferous tubule (spermiation)  Golgi forms acrosomal vesicle  acrosomal vesicle spreads over nucleus & distal centriole forms early flagellum  nucleus & cytoplasm elongate  mitochondria form midpiece, cytoplasm is shed & principle piece (tail) matures Senger 2005  Productivity:  unlimited: - puberty to death (400 million sperm/day) - spermatogonia replenished via mitosis  continuous: - continuous meiosis - asynchronous continuous production  symmetrical division: - 4 functional gametes Marieb & Hoehn 2010  sex of offspring depends on sex chromosomes (X & Y):  females have XX  males have XY  a single gene on Y chromosome, sex determining region on the Y (SRY), controls ‘maleness’ genetic sex (XY or XX) determines gonadal sex (testis or ovary) determines phenotypic sex (internal & external genitalia)  Spermatogonium Meiotic events Before birth XX Oogonium XY XY Type A daughter cell Mitosis Mitosis XY XX Primary oocyte Type B daughter cell Growth Growth Infancy and childhood XX Primary oocyte XY Primary (ovary inactive) Meiosis I spermatocyte Each month from X Y Secondary puberty to spermatocytes menopause Meiosis II XX Primary oocyte X X Y Y Early spermatids sex Late spermatids determined Spindle XX X X Y Y by sperm Meiosis I Secondary oocyte First polar body X X Ovulation Spermatozoa Meiosis II of Sperm 1 X-bearing Polar body X X X Y Y Meiosis II 2 X-bearing Polar bodies X X X X Marieb & Hoehn 2010 2 Y-bearing (all polar bodies degenerate) Second polar body Ovum  Marieb & Hoehn 2010 Gametogenesis is largely regulated by hormones → endocrine system  Hormones are chemical signals for communication (& action) between cells  Gonadotrophin releasing hormone (GnRH):  stimulates secretion of LH & FSH  Luteinizing hormone (LH):  stimulates secretion of testosterone  Follicle stimulating hormone (FSH):  supports Sertoli cell function  Androgen Binding Protein (ABP)†:  sequesters T to site of spermatogenesis  Testosterone (T):  essential for initiation of spermatogenesis  stimulates primary & secondary sex characteristics  Inhibin:  regulates rate of spermatogenesis (~20 million/ml) by inhibiting FSH † not a true hormone  inhibin specifically Leydig cell inhibits FSH (not GnRH) Sertoli  head:  acrosome: digests zona pellucida  compact nucleus: delivery of chromosomes  midpiece:  mitochondria: powerhouse of motility  tail:  microtubule doublets: flexure for propulsion Johnson 2007  Ejaculated sperm cannot immediately fertilize oocyte  Need to spend several hours in female reproductive tract to attain capacity to fertilise  Oestrogen & vaginal mucus destabilize the sperm plasma membrane & trigger hyperactive motility  Process involves:  removal of protein coating acquired in epididymis  reorganization of plasma membrane to expose binding sites Senger 2005  www.mysbfiles.stonybrook.edu  Swelling of acrosome & fusion of outer acrosomal membrane with overlying plasma membrane  Calcium-dependent event: ↑ intracellular Ca2+ & cAMP  Stimulated by progesterone & a protein (ZP3) on the zona pellucida that surrounds the oocyte  Release of digestive enzymes from acrosome:  hyaluronidase → cumulus cell penetration  acrosin → zona pellucida digestion Acrosome-reacted sperm have a very short lifespan!  Marieb & Hoehn 2010 Sperm Corona  capacitation: oestrogen/mucus radiata destabilize sperm PM & hyperactivate motility Zona pellucida ZP3 molecules  acrosome reaction: progesterone & Oocyte plasma binding to ZP3 causes ↑Ca2+ & release of membrane Oocyte sperm-binding digestive enzymes from sperm receptors  fertilization: sperm digests zona, Cortical binds to sperm-binding receptor & fuses granules with oocyte PM Acrosomal process  polyspermy block: fusion causes ↑Ca2+ & electrical block of oocyte PM Cortical reaction (fast block), then cortical granule release Sperm which hardens zona & removes sperm- nucleus binding receptors (slow block) Only single sperm needed to fertilize an oocyte!!  Testes secrete several male sex hormones (androgens):  testosterone (most abundant)  dihydrotestosterone  androstenedione  Testosterone is formed by the Leydig cells which account for ~20% of adult testis mass Johnson 2007 Responsible for spermatogenesis & characteristics that define the masculine body  Production increases rapidly during puberty due to decreased responsiveness of the hypothalamic – pituitary axis to negative feedback  Development of male primary sexual characteristics:  penis, scrotum & testes (8-fold ↑ by 20 y.o.)  prostate gland  seminal vesicle  male genital ducts (incl. epididymis & vas deferens) Jones & Lopez 2006  Development of male secondary sexual characteristics:  body hair – over abdomen, face & chest  baldness – decreased growth of hair on top of head  voice – hypertrophy of laryngeal mucosa & enlargement of larynx  skin – increased thickness, increased sebaceous gland secretions & acne  muscles – protein formation & muscle development  bone – increase bone matrix & Ca2+ retention  metabolism – increased basal metabolism  behaviour – promotes sex drive (libido) & aggressiveness