Lecture 5 Embryology Reproductive System PDF

Learning outcomes Describe the embryology of the reproductive system by describing the development of the following in both males and females: Gonads Genital ducts External genitalia Chapter 16, Sixth Edition. Available...

Learning outcomes Describe the embryology of the reproductive system by describing the development of the following in both males and females: Gonads Genital ducts External genitalia Chapter 16, Sixth Edition. Available on ClinicalKey (through library databases)  DEVELOPMENT OF THE REPRODUCTIVE SYSTEM OVERVIEW  Watch animation here: https://www- Overview clinicalkey-com.ez.sun.ac.za/#!/content/book/3- s2.0-B9780323696043000167 Gonadal ridge from intermediate mesoderm. Germ cells migrate from yolk sac to mesenchyme medial to mesonephri. Induces formation of somatic support cells (Sertoli , follicle ). Formation of paramesonephric ducts lateral to mesonephric ducts. Development as male/female depends on genes: Y chromosome. SEX DETERMINATION Sex determination Determined at fertilization. https://scitechconnect.elsevier.com/sex-genes-y- End week 6: SRY gene on Y chromosome chromosome-future-of-men/ expressed in somatic support cells. Absence of this gene = develop as female. SRY gene encodes SRY protein (transcription factor) – development of testes (gonadal sex determination) - male genital ducts & glands, male external genitalia, male secondary sex characteristics. https://www.semanticscholar.org/paper/Penile-Embryology- and-Anatomy-Yiee- Baskin/07a1e6d3ad2fd21440d876209ff695f3c02fc1de  Sex determination in developing gonad (male) SRY protein: somatic support cells develop into pre- Sertoli cells. These induce subset of interstitial stroma cells: into Leydig cells & peritubular myoepithelial cells. Sertoli cells envelop the germ cells. Organise into testis cordis with the myoepithelial cells: Future seminiferous tubules. Deepest somatic support cells: no germ cells Form rete testis – connects seminiferous tubules to the mesonephric duct.  Sex determination in males Nephric tubules – form efferent ductules of tetes Mesonephric ducts – become epididymis and vas deferens. Paramesonephric ducts degenerate. During 3rd month of development, seminal vesicle develops from the distal vas deferens. Prostate and bulbourethral glands grow from pelvic urethra. External genitalia (up to now “indifferent”): differentiate into penis and scrotum. Late in fetal development: testes descend into scrotum through inguinal canals.  Sex determination in females No SRY gene = no SRY protein Somatic support cells form follicle cells surrounding germ cells: Forms primordial follicles of the ovary. Mesonephric ducts degenerate. Paramesonephric ducts become genital ducts: Proximal parts: uterine tubes Distal ends fuse: uterus Vagina formed from vaginal plate: outgrowth of urogenital sinus Indifferent external genitalia: clitoris, paired labia majora & minora  Couple expecting a baby boy (based on ultrasound) – told at birth that baby is a girl. Baby has “ambiguous genitalia” – enlarged clitoris, separate urethra and vagina, partial fusion of the labia. Gonads are palpable in the groin. Tests reveal normal testosterone and luteinizing hormone levels. Clinical Case Ultrasound: no cervix, uterus, uterine tubes. Gonads in inguinal canal. Genetic tests: XY chromosome (46 XY). Diagnosis of androgen insensitivity syndrome: mutation in androgen receptor gene, less responsive to testosterone. Genetic, gonadal & phenotypic sex may be discordant. FORMATION OF GENITAL RIDGES  Formation of genital ridges 5th week: primordial germ cells migrate from the yolk - via dorsal mesentery – to mesenchyme of posterior body wall – near T10. Moves to adjacent coelomic epithelia – medial, ventral and superior to the developing mesonephric kidneys. Coelomic epithelia proliferate, thicken and form pair of genital ridges (includes the primordial germ cells).  Formation of genital ridges Week 6: coelomic epithelial cells – form somatic support cells and interstitial stromal cells. Somatic support cells – invest the germ cells – essential for their development. At end week 6: male and female – indistinguishable (ambisexual/bipotential). After week 6: support cells differentiate between males and females (sex determination slides). From week 7: males and female structures begin to differentiate.  FORMATION OF PARAMESONEPHRIC DUCTS  Formation of paramesonephric ducts Week 6: Paramesonephric ducts – form lateral to mesonephric ducts: Invagination of thickened proliferating coelomic epithelial cells From third thoracic segment to posterior wall of urogenital sinus (craniocaudal direction). Caudal tips: fuse & connect with developing pelvic urethra (medial to openings of mesonephric ducts). Cranial ends: form funnel shaped openings into coelom. Homologous structures in the male and female Diverge from week 7. MALE GENITAL DEVELOPMENT  Watch animation here: https://www-clinicalkey- Male Genital Development com.ez.sun.ac.za/#!/content/ book/3-s2.0- B9780323696043000167 SRY protein expressed in somatic support cells. Differentiate into Sertoli cells – envelop the germ cells. Male Genital Development  Male Genital Development Week 7: Sertoli cells & interstitial cells – form testis cords. Germ cells in the center of the cords. Testis cords differentiate into seminiferous tubules at puberty. In region next to mesonephros (no germ cells present) – Sertoli cells organize into ducts called rete testis. At puberty, rete testis forms conduit between seminiferous tubules and mesonephric tubules (efferent ductules). Mesonephric ducts – develop into epididymis, vas deferens, & seminal vesicles. Testis become rounder, coelomic epithelium is separated from testis cordis by tunica albuginea (connective tissue layer).  Male Genital Development – Regression of paramesonephric ducts Sertoli cells secrete glycoprotein hormone - anti- Müllerian hormone (AMH) (or Müllerian- inhibiting substance (MIS)). Sertoli cells also prohibit germ cell development. Causes paramesonephric ducts to regress between weeks 8 and 10. Remnants of paramesonephric ducts in males: Appendix testis – small cape of tissue. Prostatic utricle – expansion of prostatic urethra. Week 9-10: Leydig cells differentiate from interstitial stromal cells. Produce testosterone – persistence of mesonephric duct (forms male genital tract).  Watch animation here: Male Genital Duct and https://www-clinicalkey- Accessory gland development com.ez.sun.ac.za/#!/content /book/3-s2.0- Weeks 8-12: testosterone secretion stimulates B9780323696043000167 mesonephric ducts to differentiate: Epididymis, vas deferens, ejaculatory duct. Connect testes with urethra. Accessory glands develop near junction between mesonephric ducts and urethra: Seminal vesicles (week 10) from mesonephric duct near attachment to urethra. Ejaculatory duct – portion of vas deferens (mesonephric duct) between seminal vesicle and urethra Male Genital Duct and Accessory gland development Prostate gland: week 10 – endodermal evaginations from urethra. Induced by surrounding mesenchyme to form solid cords. Week 11: cords develop a lumen and glandular acini/ Weeks 13-15: begins secretory activity (as testosterone concentration is high). Mesenchyme surrounding the glandular portion – differentiates into smooth muscle and connective tissue. During same time: bulbourethral glands develop from urethra (inferior to prostate). FEMALE GENITAL DEVELOPMENT  Watch animation here: Female Genital Development https://www-clinicalkey- com.ez.sun.ac.za/#!/content Absence of SRY – somatic support /book/3-s2.0- cells differentiate into follicle cells B9780323696043000167 (granulosa cells) and thecal cells (Leydig homologue). Absence of testosterone and anti- Müllerian hormone (AMH): Male genital ducts not stimulated to develop (mesonephric ducts & tubules regress). Paramesonephric ducts persist – differentiate into uterine tube, uterus, part of vagina.  Female Genital Development Somatic support cells: do not inhibit germ cell development Germ cells differentiate into oogonia, which proliferate. Differentiate into oocytes – enter 1st meiotic division. Pre-follicle cells (somatic support) – surround individual oocytes to form primordial follicles. Follicles localize to cortical region of ovary. Medullary region – blood supply, nerves, connective tissue. Follicle cells – arrest further oocyte development until puberty.  Watch animation here: Female Genital Duct Development https://www-clinicalkey- com.ez.sun.ac.za/#!/content /book/3-s2.0- Caudal ends of paramesonephric ducts: fused before contacting posterior wall of B9780323696043000167?scr urogenital sinus. ollTo=%23f0080 Urethral wall forms thickening – sinusal tubercle. When fused tip of paramesonephric duct connects with sinusal tubercle: Paramesonephric ducts start to fuse from caudal to cranial. Forms short tube with lumen. Tube forms uterus Cranial, unfused portions – uterine tubes Cranial openings – infundibula of uterine tubes Female Genital Duct Development Vagina derived from expansion of sinusal tubercle. Expands into solid block of endodermal tissue: vaginal plate Lengthens and sheds cells to form lumen. Months 3-4: Lower end lengthens Junction with urogenital sinus translocated caudal Rests on posterior wall of urogenital sinus Opens separately from urethra into vestibule. Endodermal membrane separates vaginal lumen from urogenital sinus (which forms vestibule of vagina). Degenerates after 5th month, remnant persists as hymen.  DEVELOPMENT OF EXTERNAL GENITALIA Development of external genitalia Early development similar in males and females. Urorectal septum: separates urogenital sinus and anorectal canal. Mesoderm anterior and cranial to the phallic segment of urogenital sinus expands – forming the genital tubercle. Genital tubercle forms phallus. Cloacal membrane ruptures – floor of the phallic segment of urogenital sinus is lost. Roof expands along lower surface of genital tubercle as it enlarges: Forms the urogenital plate Distal end: remnants of cloacal membrane remain as glans plate.  Development of external genitalia Week 5: pair of swellings (urogenital folds) – develop on either side of urogenital plate – expansion of mesoderm underlying ectoderm. Folds meet and join the genital tubercle. Anal folds – expansion of underlying mesoderm by anal folds. Labioscrotal swellings appear on either side of urogenital folds. Male and female genitalia: similar until end of week 12 (indifferent stage).  Development of external genitalia - male Week 6: urethral groove forms along ventral surface of urogenital plate as genital tubercle elongates. Initially urethral groove and folds only extend along part of shaft of elongating phallus. Distally – terminate at solid glans plate.  Development of external genitalia - male As phallus elongates – urethral folds grow towards one another & fuse in midline (from perineal region towards glans). Converts urethral groove into tubular penile urethra. Solid glans plate cannalises and joins the developing penile urethra to form the glans urethra and external penile meatus. 4th month: dihydrotestosterone effects – perineal region separating urogenital sinus from anus lengthens. Labioscrotal folds fuse at midline to form scrotum Urethral folds fuse to enclose penile urethra (complete by 14 weeks).  Development of external genitalia - female Absence of dihydrotestosterone: genital tubercle does not lengthen. Labioscrotal and urethral folds do not fuse across midline. Phallus bends inferior and becomes the clitoris. Phallic portion of urogenital sinus becomes vestibule of the vagina. Urethral folds becomes labia minora. Labioscrotal swellings become labia majora.  FORMATION OF INGUINAL CANAL & DESCENT OF GONADS  Watch animation here: Mesonephric-gonadal complex https://www-clinicalkey- com.ez.sun.ac.za/#!/content/b within abdomen ook/3-s2.0- B9780323696043000167 Segregates from the adjacent intermediate mesoderm – remains anchored by two ligaments: Cranial suspensory ligament: extends to the diaphragm. Gubernaculum (caudal genito-inguinal ligament): extends to peritoneal floor – attached to the fascia between the external and internal oblique abdominal muscles in region of labioscrotal swellings.  Development of Inguinal Canals Evagination of the peritoneum develops on three sides of the gubernaculum, forming a blind-end cavity – vaginal process. Grows inferiorly, pushing out evagination consisting of the layers of the abdominal wall – forms inguinal canal (testes descend in males) and spermatic cord layers: Transversalis fascia – internal spermatic fascia. Internal oblique muscle and fascia – cremasteric fascia. External oblique muscle and fascia – external spermatic fascia. Superior ring – deep ring of inguinal canal Inferior ring – superficial ring Females – vaginal process remains rudimentary, usually degenerates.  Descent of Gonads - Testes Both testes and ovaries descend from original position at T10. Gubernaculum = guide for the descent, forms in week 7. Weeks 7th – 12: extrainguinal part shortens and pulls testes down to deep inguinal ring (intra-abdominal phase). At the same time, the cranial suspensory ligament regresses.  Descent of Testes Testes remain at deep ring: months 3 – 7, then enter inguinal canal – gubernaculum shortens and migrates (inguinoscrotal phase). Testes remain within fascia of vaginal process and descend towards scrotum (aided by increased abdominal pressure from abdominal viscera growth). Shortly before birth – testes are within scrotal sac and gubernaculum reduced to small ligamentous band attaching caudal pole to scrotal floor. Cranial portion of vaginal process obliterated – tunica vaginalis remains.  Descent of ovaries Gubernaculum does not shorten or swell like in males – but ovaries do still descend during month 3. Ovary becomes swept out into peritoneal fold – broad ligament of the uterus: - When gubernaculum becomes attached to developing paramesonephric ducts on posterior abdominal wall. - As paramesonephric ducts fuse together to form uterus, ovaries are pulled into peritoneal folds. Absence of male hormones: gubernaculum remains intact Forms round ligament of the uterus and (round) ligament of the ovary. Cranial suspensory ligament also persists. Descent of ovaries RECAP  Development of reproductive system: summary Primordial germ cells migrate from yolk sac to genital ridges. Somatic support cells (coelomic epithelium) -development of testes/ovary Paramesonephric ducts develop. Males: mesonephric ducts – genital ducts paramesonephric degenerate Females: mesonephric ducts degenerate Paramesonephric ducts form genital ducts External genitalia: genital tubercle, labioscrotal swellings Thank you for your attention