Introduction to Male Reproductive Processes - PDF

Introduction to… Male Reproductive processes MEDI11-102 Dr Jacob Thorstensen Assistant Profess...

Introduction to… Male Reproductive processes MEDI11-102 Dr Jacob Thorstensen Assistant Professor, Medicine [email protected] CRICOS Provider Code: 00017B TEQSA: PRV12072 ATTENDANCE Have you checked in? Please remember to check into the session via Osler!  What are our objectives for today? Describe and explain the: LO1) Processes of spermatogenesis and spermiogenesis Role of sustentacular (Sertoli) and interstitial (Leydig) cells LO2) Endocrine regulation of spermatogenesis Actions of GnRH, FSH, LH, ABP and testosterone LO3) Anatomy and functional anatomy of the male reproductive tract Transport of sperm through the male reproductive tract (and major structures of the tract) Components of semen (and contributions of accessory glands) LO4) Processes of sperm maturation in the female reproductive tract and fertilisation Capacitation, acrosome reaction and block to polyspermy Major events of fertilisation LO1) Processes of spermatogenesis and spermiogenesis LO1) Processes of spermatogenesis and spermiogenesis Sagittal cut of one testicle Testis has two main functions: 1. Sperm production 2. Androgen production Spermatic cord* (testosterone) Seminiferous Is temperature important? Epididymis tubules (storage) Yes! Sperm production occurs at (production) temperatures 2-3oC below body *The spermatic cord contains: temperature! But how is this Ductus (vas) deferens possible? Testicular artery Dartos Pampiniform plexus muscle Testicular nerve Cremaster muscle LO1) Processes of spermatogenesis and spermiogenesis Let’s look at a single seminiferous tubule Three key cells: 1. Sustentacular (aka Sertoli, inside the seminiferous tubule) → Produce Androgen Binding Protein (ABP) and Inhibin → Stimulated by Follicle Stimulating Hormone (FSH) Lumen 2. Interstitial cells (aka Leydig, outside the seminiferous tubule) → Produce Testosterone → Stimulated by Luteinizing Hormone (LH) 3. Spermatogenic cells (which are spermatogonium stem cells, inside the seminiferous tubule) → Turn into sperm LO1) Processes of spermatogenesis and spermiogenesis Spermatogenesis and spermatogenic cells Can you tell the difference? Spermatogenesis = Stem cell → mature sperm Spermiogenesis = Spermatid → mature sperm (i.e., final part of spermatogenesis) LO1) Processes of spermatogenesis and spermiogenesis Spermiogenesis (phenotypic maturation) 1. Acrosomal enzymes packaged by Golgi apparatus 2. Acrosome forms at one end, centrioles gather at the opposite end 3. Microtubules elaborate to form flagellum 4. Mitochondria multiply 5. Excess cytoplasm shed 6. Immature sperm structure 7. Mature sperm structure LO1) Processes of spermatogenesis and spermiogenesis Sustentacular (Sertoli) cells Form wall of seminiferous tubule to “surround” and protect sperm Form tight junctions (between cells, and between basal and adluminal compartment) = blood-testis barrier Immunity? Secrete nutrients and testicular fluid Remember: release Inhibin and ABP LO2) Endocrine regulation of spermatogenesis LO2) Endocrine regulation of spermatogenesis Hypothalamus releases GnRH, which stimulates anterior pituitary gland to release FSH & LH Testis LH stimulates interstitial cells to produce testosterone FSH stimulation of all functions of sustentacular cells including inhibin and ABP production Testosterone stimulates spermatogenesis ABP binds, concentrates/traps testosterone to bath spermatogenic cells Negative feedback Inhibin reduces FSH release Testosterone reduces FSH, LH and GnRH release LO2) Endocrine regulation of spermatogenesis Other actions of testosterone? Across the lifespan Highest levels in teenage years and adolescence Stimulates growth of reproductive organs to adult size at puberty Levels decline with increasing age Reduced size of testes, decreases in libido, lower bone and muscle mass, increased fat mass, decreased erythropoiesis Testosterone affects the brain Androgen receptors expressed in the CNS Underlies sex drive Male secondary sex characteristics Deepening of voice Male pattern of body hair growth Skeletal muscle hypertrophy Increased heaviness of skeleton LO2) Endocrine regulation of spermatogenesis Check out the video I made for LO2: Link: https://www.youtube.com/watch?v=n49ikIr4S0U LO3) Anatomy and functional anatomy of the male reproductive tract LO3) Anatomy and functional anatomy of the male reproductive tract Structures LO3) Anatomy and functional anatomy of the male reproductive tract Functions A. Site of spermatogenesis B. Site of sperm storage C. Ducted network of the male tract (transport) Seminal D. Accessory glands F C (secretions) D Prostate E. Interconnections: Bulbourethral accessory glands & ducted network (transport) F. Interconnection: E reproductive tract & urinary tract (transport) B A LO3) Anatomy and functional anatomy of the male reproductive tract Accessory gland secretions – sperm needs a transport medium! Seminal vesicle Prostate Bulbourethral gland 1. Fructose: serves as an energy 1. Citric acid: Serves as an energy 1. Releases a mucous that serves source for sperm. source for sperm. as a lubricant for the urethra. 2. Prostaglandins: improves 2. Zinc, calcium and magnesium: 2. Bicarbonate: neutralizes acids sperm motility and facilitates maintains sperm motility. within the urethra and female uterine contractions. 3. Prostate specific antigens: reproductive tract. Decreases viscosity of plays a role in the dissolution secretions in female of the seminal fluid coagulum reproductive tract. later. 3. Semenologins: clotting 4. Relaxin: improves sperm proteins that give semen a motility. gel-like consistency (and prevents premature capacitation). 4. Ascorbic acid: serves to protect sperm from oxidative damage. NOTE: Semen = Spermatozoa + testicular fluid + accessory gland secretions LO4) Processes of sperm maturation in the female reproductive tract and fertilisation LO4) Processes of sperm maturation in the female reproductive tract and fertilisation From site of sperm production to site of fertilisation* Copulation: deposition of semen within the female reproductive tract (vagina) Sperm transported from testis to oviduct Travel 30-40 cm within male and female tract Within minutes-hours sperm reach oviduct (site of fertilization) Motility agents and uterine contractions achieve this In female tract there is further sperm development Freshly deposited sperm incapable of fertilizing an oocyte Requires 1) capacitation and 2) acrosome reaction (when in contact with the oocyte) *Fusion of gametes to produce zygote (sperm and egg combine) LO4) Processes of sperm maturation in the female reproductive tract and fertilisation Capacitation Sperm acquires ”full capacity” and is ready to fertilise! Occurs upon exposure to secretions from the female reproductive tract (e.g., uterine walls) Destabilises the plasma membrane of sperm Prepares the sperm for Increases calcium acrosome reaction (i.e., permeability to increase exposure of proteolytic motility (increases strength enzymes in sperm head) of speed of flagellum) LO4) Processes of sperm maturation in the female reproductive tract and fertilisation Acrosome reaction Why? Stops cross species fertilisation! At zona pellucida: sperm interacts with proteins on egg cell, causes Ca2+ release Release of enzymes that degrade the zona pellucida (hyaluronidase, acrosin, proteases and others) 100s of sperm needed! Block to polyspermy Why? Stops polyploidy! Fast (Na+) versus slow (Ca2+) block Slow block: Exocytosis of cortical granules Release enzymes to breaks down sperm receptors on egg LO4) Processes of sperm maturation in the female reproductive tract and fertilisation Major events following acrosomal reaction LO4) Processes of sperm maturation in the female reproductive tract and fertilisation Why are so many sperm produced? Hundreds of millions deposited in the vagina but ~50% leak out Many sperm die in the acidic vaginal environment (even with male accessory gland secretions!) Cervix acts as a major barrier to entry to the uterus Uterine contractions are strong! Assist in sperm transport (reverse peristalsis) but destroy many sperm! Hundreds of sperm are needed to penetrate the egg But only one sperm’s nuclear material is required for fertilization