Genital Embryology (1).pdf

Genital Embryology Gonads Sex/reproductive glands (Testis, ovaries) 3 primary cell types: o Mesenchymal cells o Mesothelial cells o Primordial germ cells Develop in gonadal ridge at 7 wks Derived from mesenchyme (mostly mesoderm) Primordial germ cells derived from epiblast o Migrate from the wall of...

Genital Embryology Gonads Sex/reproductive glands (Testis, ovaries) 3 primary cell types: o Mesenchymal cells o Mesothelial cells o Primordial germ cells Develop in gonadal ridge at 7 wks Derived from mesenchyme (mostly mesoderm) Primordial germ cells derived from epiblast o Migrate from the wall of the yolk sac to the gonadal ridge o Invade gonadal ridges, settle into the primary sex cords Failure to reach ridges: gonads do not develop Male/female gonads initially identical o Indifferent gonad (not yet testis/ovary) Gondal Ridge Cell Types Fate Gonadal ridge medulla: Male = Leydig cells Female = ovarian support stroma Mesothelial Cells Gonadal ridge and primary sex cord cortex: tubes Male = seminiferous tubules Female = ovarian follicles Primordial Germ Cells Enter primary sex cords as future gametes: Sperm/egg Male = spermatogonia Female = oogonia Cell Type Mesenchymal Cells Testis SRY gene on Y chromosome determines MALE o Not activated until the 7th week of gestation Produce testis determining factor (TDF) – testis development Forms Sertoli and Leydig cells o Sertoli cells secrete Mullerian inhibitor factor (MIF) o Leydig cells secrete testosterone Testosterone -> male development Medullary (testis) cords form Expand out of testis à connect to genital ducts Mullerian-Inhibiting Substance From Sertoli cells Paramesonephric duct suppressed: NO female organ (ovary, uterus) Testosterone From Leydig Cells Forms “SEEDE” o Seminal Vesicles o Epididymis o Ejaculatory duct o Ductus (vas) deferens o Efferent Ductules Ovary Absence of SRY leads to the formation of ovaries o Ovary-determining gene is WNT4 o When WNT4 is present and SRY is absent, the embryo develops female characteristics Medullary cords regress Cortical cords develop à form clusters Surround germ cells Oogonia and follicular cells form primordial follicles (imp for gonads) Estrogens contribute to formation of: o Paramesonephric ducts (form female internal structure) Only occurs in the absence of MIF and androgens § Uterine tubes § Uterus § Upper vagina (2/3) o External Genitalia § Labia § Clitoris § Lower Vagina Internal Genitalia Genital ducts develop into internal genital tracts at 8 weeks Embryo has both pairs of ducts- Wolffian and Mullerian- (one will stay, other will disappear) o Decides if embryo is male or female Mesonephric (wolffian) – male internal structures o Epididymis o Vas Deferens Anti-Mullerian Hormone (AMH) deficiency o Seminal vesicle Rare disorder of sex development in pt with an XY genotype o Ejaculatory Ducts Internal female genital ducts (lack of Müllerian duct involution) Paramesonephric (Mullerian) – female internal structures Normal external male o Fallopian tubes Normal internal male (due to androgens) o Uterus Patients are at increased risk of cryptorchidism due to o Upper Vagina tethering of the testicle by Müllerian duct–derived structures during in-utero descent from the abdomen to the scrotum; an Male Genital Ducts associated inguinal hernia can also occur Sertoli cells: Müllerian inhibitory factor (MIF) o Suppress development of paramesonephric ducts o Male remnant: appendix testis (tissue at upper testis) Leydig cells: Androgen that stimulate development of mesonephric ducts Mesonephric (Wolffian) ducts form male internal structure: o Epididymis § Duct behind testis § Transport sperm from seminiferous tubules to vas deferens o Ductus (vas) deferens: Transport sperm from epididymis to ejaculatory ducts o Seminal vesicles § Glands behind the bladder § Secrete about 75% of fluid in semen § Connect with ejaculatory ducts o Ejaculatory ducts § Collect sperm/fluid from seminal vesicles and vas deferens § Pass through prostate § Connect to urethra Summary Embryo begins Bipotential gonad. Wolffian (blue) and Müllerian (red) ducts are present Y chromosome, the gonads of the bipotential urogenital ridge differentiate into testes, which produce both MIS to eliminate the Müllerian ducts and testosterone to stimulate differentiation of the Wolffian ducts into the male internal reproductive tract structures In the absence of SRY, ovaries differentiate, Wolffian ducts degenerate, and Müllerian ducts develop into a simple columnar epithelial tube that will differentiate into the oviducts, uterus, cervix, and upper portion of the vagina. Urogential Sinus Cloaca divides o Forms urogenital sinus and anal canal Urogenital sinus forms male/female some internal structures Males o Upper portion: bladder o Pelvic (middle) portion: prostate and prostatic urethra o Phallic portion: penile urethra Females o Upper portion: bladder o Pelvic portion: Inferior vagina o Connects with paramesonephric ducts Uterine Anomalies ↓ Fertility, ↑ pregnancy complication risk Septate uterus (B) o Most common o Incomplete resorption of septum o Common anomaly o Treat with septoplasty Bicornuate uterus (C) o Incomplete fusion of Müllerian ducts Uterus didelphys (D) o Mullerian ducts fail to fuse -> double uterus, cervix, vagina Summary Cloaca divides Anal canal Urogenital sinus derives some internal structures: o Males § Upper portion: bladder § Pelvic (middle) portion: prostate and prostatic urethra § Phallic portion: penile urethra o Females § Upper portion: bladder § Pelvic portion: Inferior vagina § Connects with paramesonephric ducts External Genitalia Until about the 9th week of gestational age, the external genitalia of males and females look the same Fully developed by the 12th week 5α-reductase Deficiency (male internal, Female external) Four key structures: Pathogenesis: o Genital tubercle o 46,XY genotype o Urogenital sinus (from cloaca) o Impaired conversion of testosterone to DHT o Urogenital folds (from cloaca) o Impaired virilization during embryogenesis o Labioscrotal (genital) swellings o Normal male testosterone & estrogen levels Clinical Features: MALE (external) o Male internal genitalia (eg, testes, vas deferens) Genital tubercle elongates -> penis o Female external genitalia (eg, blind-ending vagina) Urogenital folds close -> penile urethra o Phenotypically female at birth Urogenital sinus -> glands o Virilization at puberty (↑ testosterone) o Prostate gland § Clitoromegaly o Bulbourethral glands (of Cowper) § Increased muscle mass Labioscrotal swelling à scrotum § Male pattern hair development Requires dihydrotestosterone (DHT) § Nodulocystic acne o Testosterone à DHT o Enzyme: 5α-reductase DHT affects the development of the prostate, penis, and scrotum 5α-reductase deficiency o Ambiguous genitalia until puberty o At puberty: ↑ testosterone Congenital anomaly of male urethra o Hypospadia § Abnormal opening of the urethra along the inferior side of the penis § Failure of urethral folds to close during development § Cryptorchidism in ~10% of patients § Hypospadias is more common than epispadias § Abnormal opening of penile urethra on ventral (under) surface due to failure of urethral folds to fuse. o Epispadia § Congenital anomaly of male urethra § Abnormal opening of the penile urethra on the dorsal side of the penis § Much less common than hypospadias § Abnormal position/formation of genital tubercle § Commonly occurs with bladder exstrophy § Abnormal opening of penile urethra on dorsal (top) surface due to faulty positioning of genital tubercle FEMALE (external) Lack of testes reduced levels of androgens leads to the development of the lower vagina and labia Genital tubercle elongates à clitoris Urogenital folds (no fusion) à labia minora Urogenital sinus (from cloaca) à glands o Paraurethral glands (Skene) o Bartholin glands Labioscrotal swelling à labia majora Requires estrogen > androgen Acted on by Dihydrotestosterone Penis Penile Urethra Cowper and Prostate Gland Scrotum Male/Female Genital Homologs Genital Homolog Genital tubercule Urogenital folds Urogenital sinus Labiosacral Swelling Acted on by Estrogen Clitoris, Vestibular bulb Lamina minor Paraurethral and Bartholin glands Labia majora Klinefelter Syndrome (47, XXY) Genetically male Aneuploid genetic condition Additional copy of the X chromosome Most common chromosomal disorders Symptoms: o Testicular atrophy o Infertility o Gynecomastia (breast growth) o Female distribution of hair o Low testosterone o Elevated FSH and LH o High-pitched voice Turner Syndrome (45, XO, or 45X) Genetically female Partially or completely missing an X chromosome Symptoms (without hormone treatment) o Do not develop menstrual periods o Do not develop breasts o Infertility o Congenital heart defect Short stature Edema of wrists and ankles in newborn Cystic hygroma in utero resulting in excess nuchal skin and “webbed” neck Lecture questions Boy, penis appears normal but testes are not palpable. Epididymis and Vas deferens identified. Gonads appear to be fallopian tubes and uterus Anti-mullerian hormone Girl, Tanner stage 1 breasts (no breasts). Epididymes, Testes, and Vas deferens are present 5 alpha reductase deficiency