male rep system.docx

Chapter 21 Male reproductive system: testes, genital ducts, accessory glands, penis Testes: produce sperm + endocrine cells secrete hormones (eg testosterone) for male reproductive physiology Testosterone: for spermatogenesis, sexual differentiation in embryonic + fetal development, control gonadotr...

Chapter 21 Male reproductive system: testes, genital ducts, accessory glands, penis Testes: produce sperm + endocrine cells secrete hormones (eg testosterone) for male reproductive physiology Testosterone: for spermatogenesis, sexual differentiation in embryonic + fetal development, control gonadotropin secretion in pituitary Dihydrotestosterone: metabolite of testosterone, begin to act on tissues during puberty (eg, male accessory glands + hair follicles Genital ducts + accessory glands produce secretions for sperm activity, contract to propel spermatozoa + secretions from penile urethra. Secretion: nutrients for spermatozoa in reproductive tract Semen: spermatozoa + secretion accessory glands – introduced into female reproductive tract by penis Testis: Surrounded by dense CT capsule: tunica albuginea – thickens on posterior side = mediastinum testis From this fibrous region, septa penetrate + divide it = 250 pyramidal compartments: testicular lobules Lobules have sparse CT w/ endocrine interstitial/Leydig cells – secrete testosterone, + 1-4 highly convoluted seminiferous tubules (sperm production here) Develop retroperitoneally in dorsal wall embryonic abdominal cavity + moved during fetal development suspended in 2 halves of scrotal sac/scrotum, at ends of spermatic cords In migration from abdominal cavity: each testes carries serous sac – tunica vaginalis: derived from peritoneum Tunica vaginalis: outer layer parietal layer lining scrotum + inner visceral layer; covers anterior + laterals sides testes Evolved in cold-blooded animals: sperm formation ≠ 37 C Temp of 34 C in scrotal sac Each testicular artery surrounded by rich pampiniform plexus – w/ cooler blood from testis by countercurrent heat-exchange system Evaporation of sweat from scrotum helps heat loss Relaxation/contraction thin dartos muscle of scrotum (testes away) + cremaster muscles of spermatic cord (testes closer to body): control testicular temp Excessive accumulation serous fluid in scrotal sac: hydrocele Cryptorchidism: failure of testes to descend Note: located ductus deferens along anterior + superior sides of bladder Interstitial tissue: B/w seminiferous tubules of testes Consist of sparse CT w/ fibroblasts, lymphatics, blood vessels (incl. fenestrated capillaries) During puberty interstitial/Leydig cells develop as large round/polygonal cells w/ central nuclei + eosinophilic cytoplasm high in small lipid droplets (typical for secreting endocrine cells – testosterone) Leydig cells: produce steroid hormone testosterone – promote development 2nd male sex characteristics Testosterone: synthesized by enzymes in smooth ER + mitochondria similar to system in adrenal cortical cells Secretion by Leydig cells: triggered by pituitary gonadotropin – LH (luteinizing hormone)/Interstitial cell-stimulating hormone (ICSH) Synthesis begin at puberty as hypothalamus begins producing gonadotropin-releasing hormone Late embryonic testes: gonadotropin from placenta stimulate fetal interstitial cells = produce testosterone for developments ducts + glands Fetal interstitial cells active: 3rd + 4th month pregnancy regress + quiescent = resemble fibroblasts until puberty resume testosterone synthesis (response to pituitary gonadotropin) Interstitial cells + Sertoli cell tumour rare. Testicular cancer involve germ cell tumours – only after puberty (increase w/ cryptorchidism) Seminiferous tubules: Sperm production rate in seminiferous tubules 2x108/day in young adult Testis: 250 – 1000 seminiferous tubules in lobules 150-250 micrometers diameter, 30-70 cm length Combined length tubules in 1 testis: 250 m Surrounded by stroma w/ many interstitial cells (secrete androgens) Wall: made of germinal epithelium – made of columnar Sertoli cells + dividing spermatogenic cells (Each tubule = loop) - Straight tubules (short, narrower segment) link tubule to rete testis: labyrinth epithelium-lined channels embedded in mediastinum From rete testis sperm into epididymis 10-20 efferent ductulus connect rete testes to head epididymis Outside tubules: myoid cells + fibroblasts Lined w/ specialized stratified epithelium: germinal/spermatogenic epithelium Basement membrane of germinal epithelium: covered by fibrous CT, innermost layer w/ flattened smooth muscle-like myoid cells (around tubules) Myoid cells: allow weak contractions of tubule (move fluid + mature sperm), elongated nuclei Germinal epithelium - consist of 2 types of cells: Sertoli cells: large, non-dividing, physically + metabolically support developing sperm precursors, phagocytize debris, endocrine role - effect spermatogenesis + fetal development male reproductive tract. Columnar shape, have abundant prosaposin (glycoprotein), dendritic nature of apical ends Dividing cells of spermatogenic lineage Cells spermatogenic lineage: comprise ≥ 4 concentric layers of cells in germinal epithelium, develop from progenitor cells fully formed sperm cells (in 10 weeks) Spermatogenesis: 1st part sperm production – mainly mitosis + meiosis spermiogenesis – final differentiation process in haploid male germ cells Spermatogenesis: Begin at puberty w/ proliferation stem + progenitor cells: spermatogonia – small round cells, 12 micrometer diameter; occupy basal niche in epithelial wall tubules (near basement membrane) + associated w/ Sertoli cells surface Diff stages spermatogonia development recognize by change shape + staining properties nuclei Spermatogonia w/ dark ovoid nuclei: stem cells – divide infreguently + give rise new stem cells , + produce cells w/ pale-staining ovoid nucelei = divide more quickly as transit amplifying cells: type A spermatogonia Type A spermatogonia: ungergo unique clonal division = leave cells interconnected as syncytium become Type B spermatogonia: more spherical + pale nuclei Type B spermatogonia: final mitotic division = 2 new cells grow: primary spermatocytes: spherical cells w/ euchromatic nuclei Summary: Type A spermatogonia Type B spermatogonia after mitosis they become primary spermatocytes after meiosis they become secondary spermatocytes with only 23 chromosomes instead of 46 (they are rare in testis sections because they are very short-lived cells)after undergoing meiosis II, they become spermatids Primary spermatocytes: replicate DNA = each chromosome made of duplicate chromatids meiosis: homologous chromosome synapsis, DNA recombination, 2 cells division = haploid cells 46 chromosomes (diploid no.) + DNA content: 4N After formation meiotic prophase (3 weeks) – most seen in this phase in sections Largest cells of spermatogenic lineage Characterized: partially condensed chromosomes in stages synapsis + recombination 1st meiotic division homologous chromosomes separate = smaller cells: secondary spermatocytes w/ 23 chromosomes, made of 2 chromatids, DNA amount: 2N Secondary spermatocytes: rare in testis section, short-lived, in interphase briefly 2nd meiotic division: separate chromatids each chromosome = 2 haploid cells: 23 chromosomes (no S phase/DNA replication b/w divisions = DNA amount halved = haploid cells) Fertilization: haploid ovum + sperm (from meiosis) = normal diploid chromosome number Clonal nature of male germ cells: Stem cells produced by mitotic divisions spermatogonia remain separate cells Division daughter cells, become transit amplifying progenitor cells – incomplete cytokinesis after telophase + cells attached by intercellular bridges of cytoplasm Intercellular bridges: allow free cytoplasmic communication during mitotic + meiotic divisions 100 cells approx. remain linked during meiosis = spermatogenic syncytium Cytoplasmic bridges allow haploid cells supplied w/ products of complete diploid genome – proteins + RNA encoded by genes on X/Y chromosomes missing in haploid nuclei Germ cells separated in differentiation Cellular events + changes (b/w final mitosis spermatogonia + formation spermatids): 2 months Spermatogenic cells ≠ randomly distributed in spermatogenic epithelium Cells different stages development grouped together along tubule, intercellular bridges coordinate divisions + differentiation Spermiogenesis: Final phase sperm production Temperature sensitive process by which spermatids differentiate into spermatozoa – specialized to deliver male DNA to ovum No cell division Spermiogenesis + spermatogenesis – cells remain associated w/ Sertoli cells Haploid spermatid small (7-8 micrometer diameter) – near lumen of seminiferous tubules Includes formation acrosome, condensation + elongation nucleus, development flagellum, loss of much cytoplasm Produce mature spermatozoon – released from Sertoli cells surface into tubules lumen stages: Golgi phase: Cytoplasm: prominent Golgi apparatus near nucleus, mitochondria, paired centrioles, free ribosomes. Small proacrosomal vesicles from Golgi apparatus coalesce = single membrane-limited acrosomal cap close to one end of the nucleus. Centrioles migrate to the farthest position from acrosomal cap: 1 = act as basal body - organize axoneme of the flagellum (structurally/functionally similar to cilium) Cap phase: Acrosomal cap spreads over half of the condensing nucleus. Acrosome = specialized lysosome w/ hydrolytic enzymes (mainly hyaluronidase and a trypsin-like protease = acrosin) enzymes released when a spermatozoon encounters an oocyte + acrosomal membrane fuses w/ sperm’s plasma membrane dissociate cells corona radiata + digest zona pelliduca (both surround egg) = Acrosomal reaction: one of the first steps in fertilization Acrosome phase: Head of the developing sperm (w/ acrosome + condensing nucleus) = remains embedded in the Sertoli cells + growing axoneme extends into the lumen of the tubule. Nuclei = more elongated + highly condensed Histones of the nucleosomes replaced by small basic peptides = protamines Flagellum growth continues distally in tail. Mitochondria aggregate around flagellum proximally = form thickened middle piece – produce ATP for flagellar movement Maturation phase: Unneeded cytoplasm shed = residual body from each spermatozoon + remaining intercellular bridges are lost. Mature/fully formed ≠ functional/mobile sperm are released into the lumen of the seminiferous tubule Clinical note: decreased sperm (idiopathic) = male infertility. Common feature low sperm quality: oligospermia (low ejaculate vol.), low sperm density, abnormal morphology, flagellar defects Sertoli cells: Tall columnar epithelial cells Nourish spermatogenic cells + divide seminiferous tubules into 2: basal + adluminal compartments All spermatogenic lineage cells associated w/ Sertoli cells extended surfaces – for metabolic + physical support Adhere to basal lamina + apical ends extend to lumen Routine prep: poorly defined, surround spermatogenic cells Each supports 30-50 developing germ cells Abundant SER, some rER, well developed Golgi complexes, high mitochondria, lysosomes Nuclei: ovoid or triangular, euchromatic, prominent nucleolus Tight occluding junction’s b/w basolateral membranes = blood-testis barrier in seminiferous epithelium (tightest blood-tissue barrier) physical barrier, stop autoimmune attacks against spermatogenic cells (appear in after immune system mature + central self-tolerance established) Spermatogonia: in basal compartment of tubule, below tight junctions ≠ sealed off from vascularized interstitial tissue (w/lymphocytes + immune cells) Newly formed primary spermatocytes – temp. disassemble adhesion molecules of local occluding junctions move into tubules adluminal compartment (still adhered to S.C) All spermatocytes + spermatids (+ spermatogonia) - lie in invaginations of Sertoli cells surfaces Adluminal migration ≠ compromise blood-testis barrier (germ cells remain linked by intercellular bridges) Sertoli cells connected + coupled ionically via gap junctions – regulate transient changes in occluding junctions + synchronize spermatogenic cell activity Flagellar tails spermatocytes = look like tufts, extend form apical end S.C Sertoli cells – 3 general functions: Support, protection, nutrition of developing spermatogenic cells Spermatocytes, spermatids, developing sperm isolated from plasma proteins + nutrients via blood-testis barrier Transport or produce metabolites + nutritive factors into lumen – eg. iron-transport protein transferrin Protect spermatogenic cells from circulating immune components Supply plasma factors for growth + differentiation Exocrine + endocrine secretion: Continuously release into tubules water – carries new sperm out of testis Production nutrients + androgen-binding protein (concentrate testosterone for spermiogenesis) stimulated by FSH Endocrine cells: secrete inhibin (glycoprotein) – feedback on anterior pituitary gland suppress FSH synthesis + release In fetus: secrete Mullerian-inhibiting substance = regression embryonic Mullerian/paramesonephric ducts (absent MIS; ducts persist, parts female reproductive system) Phagocytosis: In spermiogenesis – excess cytoplasm shed = residual bodies phagocytized + digested by S.C. lysosomes No proteins from sperm pass back across blood-testis barrier Clinical notes: acute/chronic inflammation testis: orchitis – usually secondary to UTI/sexually transmitted pathogen + involve ducts connect testis to epididymis. Acute epididymitis = from STI – associated with gonorrhea infections = cause male infertility Intratesticular ducts: Straight tubules, rete testis + efferent ductules – all carry spermatozoa + liquid from seminiferous tubules to duct of epididymis Seminiferous tubules narrower straight tubules rete testis (network of channels in CT of mediastinum testis) Loops seminiferous tubules join rete testis via short straight tubules – lined initially only by Sertoli cells (no germ cells) empty into rete testis Straight tubules, near connection to rete testis – lined w/ simple cuboidal epithelium Rete testis: interconnected channels lined w/ simple cuboidal epithelium, supported by dense CT of mediastinum Rete testes drain into 20 efferent ductules – lined by alternating non-ciliated cuboidal + taller ciliated cells = scalloped appearance. Non-ciliated cells: absorb fluid secreted by Sertoli cells = absorption + ciliary activity create fluid flow carry sperm passively out of testis to epididymis Thin layer circular smooth muscles cells in walls efferent ductules = help movement sperm into duct of epididymis Efferent ductules: scalloped lining – patches simple cuboid cells w. water-absorbing microvilli alternating w/ taller cells w/ cilia Excretory genital ducts: Duct of epididymis, ductus/vas deferens, urethra Transport sperm from scrotum to penis during ejaculation Epididymis: Duct of epididymis: long, highly coiled duct, surrounded by CT, in scrotum along superior + posterior sides each testis. Surrounded by thin, circular layer smooth muscle cells – in tail region: w/ inner + outer longitudinal layers. Ejaculation: peristaltic contractions 3 muscle layers empty stored sperm in tail region – continuous w/ ductus deferens Epididymis: 6 m length. Head region: efferent ductules enter. Body: sperm cells undergo further modifications. Tail: sperm stored until ejaculations. Duct lined w/ pseudostratified columnar epithelium: made of columnar principal cells (w/ characteristic stereocilia) + small round stem cells Duct: for short term sperm storage + sperm maturation. Covered by capsule + tunica vaginalis. Lined w/ pseudostratified columnar epithelium w/ long stereocilia. Intraepithelial lymphocyes seen in epididymal duct Columnar epithelium surrounded by thin circular layer smooth muscle cells + lumen has sperm. Smooth muscle thicker + longitudinal layer in body + tail of epididymis Principal cells (epithelial cells): remove water + residual bodies enter epididymis w/ sperm, secrete protein + glycoprotein via exocytosis – change fluid in which sperm suspended. Release abundant 25-300 nm diameter exosomes + vesicles from multivesicular bodies + by apocrine secretion Passage of sperm through ducts – 2-4 weeks = spermatozoa cell membranes bind + integrate components secreted from principal cells + their exosomes (no modification ≠ sperm participate in fertilization) Changes in sperm in epididymis: Development of competence for forward motility Final acrosome modification Reorganization cell membrane surrounding sperm head: add cholesterol + decapacitation factors = block acrosomal reaction. Fertilization ability sperm inhibited until their cell membrane modified in capacitation process (in female tract) Ductus (Vas) Deferens: Long, straight tube w/ thick muscular wall + small lumen – leaves scrotum to empty in prostatic urethra Mucosa: slightly folded longitudinally – lamina propria w/ many elastic fibers + epithelial lining = pseudostratified w/ some sparse stereocilia Very thick muscularis: made of longitudinal inner + outer layer + middle circular layer – produce peristaltic contractions in ejaculation, move sperm along ductus deferens from epididymis Part spermatic cord which includes testicular artery, pampiniform plexus, nerves Follow general path along which embryonic testes descend – each ductus passes over urinary bladder = enlarges – ampulla; thicker epithelium + more folded In prostate, end 2 ampullae merge w/ ducts 2 seminal vesicles = form ejaculatory ducts – open into prostatic urethra Male contraception: vasectomy – use accessibility of ductus deferens in spermatic cord Accessory glands: Produce secretions for reproduction – mix w/ sperm in ejaculation = produce semen Seminal vesicles/glands, prostate gland, bulbourethral glands Seminal vesicles: 2 seminal vesicles : highly tortuous tubes, each 15 cm long, enclosed by CT capsule Paired exocrine glands: secrete most seminal fluid w/ sperm nutrients Mucosa: many thin, complex folds – fill lumen. Folds = lined w/ simple or pseudostratified columnar epithelial cells rich in secretory granules. Lamina propria: elastic fibers, surrounded by smooth muscle w/ inner circular + outer longitudinal layer (2 layers smooth muscle) – empty gland in ejaculation Exocrine gland – production of viscid, yellowish secretion dependent on testosterone Mucosal folds include – smooth muscle, thin lamina propria, simple columnar epithelium on principal secretory cells Fluid from seminal vesicles makes up 70% ejaculate Components of fluid: Fructose – major energy source for sperm, + inositol, citrate, other metabolites Prostaglandins – stimulate activity in female reproductive tract Fibrinogen – allow semen coagulation after ejaculation Prostate gland: Dense organ surround urethra below bladder 2 x 3 x 4 cm. Weight: 20 g Surrounded by fibroelastic capsule, septa extend from it + divide gland into indistinct lobes Function/structure depend on level testosterone (like seminal vesicles) Made of 30-50 branched tubuloacinar glands embedded in dense fibromuscular stroma (smooth muscle contracts at ejaculation) Ducts from glands can converge, all empty directly into prostatic urethra (runs through center of prostate) Glands in 3 major zones around urethra: Transition zone: 5% of prostate vol., surround superior portion urethra, has periurethral mucosal glands Central zone: 25% glands tissue, contains periurethral submucosal glands w/ longer ducts (surrounds transition zone) Peripheral zone: 70% organs tissue, has most numerous main glands w/ even longer ducts (outermost, largest zone) Tubuloacinar glands: lined – simple or pseudostratified columnar epithelium + produce fluid w/ mix exosomes, glycoproteins, enzymes, small molecules (ex. prostaglandins) – stored until ejaculation Produce prostate-specific antigen (serine protease) – liquefies coagulated semen for slow-release sperm after ejaculation. Small amount leak normally into prostatic vasculature (high level circulating PSA = abnormal glandular mucosa – prostatic carcinoma/inflammation) Corpora amylacea: mall spherical concretions (up to 2nm diameter), partially calcified, lamellar nature – in lumens of tubuloacinar glands. Contain primarily deposited glycoproteins + keratin sulfate. Increase w/ age. Clinical note - prone to 3 issues: chronic prostatitis (infectious agent involved), nodular hyperplasia/benign prostatic hypertrophy (in periurethral mucosal glands), prostate cancer (in glands peripheral zone) Bulbourethral glands: Paired, round, 3-5 mm in diameter, in urogenital diaphragm, empty into proximal part penile urethra Each gland has several lobules w/ tubuloacinar secretory units surrounded by smooth muscle cells + lined by mucus-secreting simple columnar epithelium (testosterone dependent) Erection – bulbourethral glands + very small, numerous, histologically similar urethral glands along penile urethra = secrete clear mucus-like secretions – coats + lubricates urethra (prep. For sperm passage) Penis: Consist of 3 cylindrical masses erectile tissue + penile urethra, surrounded by skin 2 erectile masses: corpora cavernosa (= dorsal) Ventral corpus spongiosum surrounds urethra, expands at end = glans Most penile urethra lined by pseudostratified columnar epithelium in glans: stratified squamous epithelium continuous w/ thin epidermis covering glans surface Small mucus-secreting urethral glands along length penile urethra Uncircumcised men – glans covered by prepuce/foreskin (retractable fold thin skin w/ sebaceous glands on internal surface) Corpora cavernosa each surrounded by dense fibroelastic layer: tunica albuginea All 3 erectile tissues = made of venous cavernous spaces lined w/ endothelium, separated by trabeculae w/ smooth muscle + CT continuous w/ surrounding tunic Central arteries in corpora cavernosa branch – form nutritive arterioles + small coiling helicine arteries to cavernous vascular spaces Arteriovenous shunts b/w central arteries + dorsal veins Penile erection: blood fills cavernous spaces in 3 masses erectile tissue. Triggered by external stimuli to CNS, controlled by autonomic nerves in vascular walls. Parasympathetic stimulation – relax trabecular smooth muscle + dilates helicine arteries = increase blood flow + fill cavernous spaces enlarge corpora cavernosa = compress dorsal veins against dense tunica albuginea = block venous outflow + produce tumescence + rigidity in erectile tissue Ejaculation: sympathetic stimulation – constrict helicine arteries + trabecular muscle = decrease blood flow into spaces = decrease pressure = veins drain blood from erectile tissue Clinical: erection dysfunction/impotence.