Embryology: Uterus, Cloaca, and Genitalia

• The lecture covers the embryology of the cloaca, uterus, and external genitalia in both males and females.
• Learning objectives include detailing sex differentiation, gonadal development, paramesonephric duct development, cloaca development into the urogenital sinus and rectum, perineal development, and common intersex states.

Indifferent Gonads

• Reproductive system development is integrated with primitive urinary organs in males and females.
• By the 6th week, the gonadal ridge develops.
• Primordial germ cells migrate from the yolk sac via the dorsal mesentery.
• These populate the mesenchyme of the posterior body wall.
• A thickened area of mesothelium develops on the medial side of the mesonephros.
• Coelomic epithelium forms somatic support cells and interstitial stromal cells, which are essential for germ cell development.

Paramesonephric Ducts

• A new pair of ducts, the paramesonephric or Müllerian ducts, form lateral to the mesonephric ducts in both male and female embryos.
• The caudal ends adhere, connect with the pelvic urethra, and cross ventral/anterior to the mesonephric ducts.
• The cranial ends form funnel-shaped openings into the peritoneal cavity.
• Germ cells and somatic support cells are present in presumptive gonads.
• Mesonephric and paramesonephric ducts are present.
• Genetic sex depends on whether the sperm carries an X or a Y chromosome.
• In XX embryos, the cortex differentiates into an ovary and the medulla regresses.
• In XY embryos, the medulla differentiates into a testis and the cortex regresses.

Male Sex Differentiation

• Sperm carries a Y chromosome, leading to an XY genetic makeup in the developing embryo.
• The presence of the SRY gene produces a protein (testis-determining factor).
• Gonadal cords differentiate into seminiferous cords.
• Sertoli cells secrete antimullerian hormone, leading to paramesonephric duct degeneration.
• Mesenchyme between cords differentiates into Lyding cells, which secrete testosterone.
• Testosterone is converted to dihydrotestosterone.
• Development includes testicular differentiation, mesonephric duct differentiation to the epididymis and vas deferens, prostate differentiation, and external genitalia differentiation into a penis and scrotum.

Development of the Testis

• The Y-chromosome's sex-determining gene produces a protein.
• This protein promotes the development of a testis.
• Primitive sex cords proliferate and penetrate the medulla, forming seminiferous tubules.
• Leydig cells secrete testosterone>>mesonephric ducts for differentiation.
• Sertoli cells regress AMH>>paramesonephric ducts.

Female Sex Differentiation

• Sperm carries an X chromosome, leading to an XX genetic make-up in the developing embryo.
• The absence of the SRY gene results in no Sertoli cells or testosterone production.
• Consequently, the paramesonephric ducts differentiate and develop, while the mesonephric ducts degenerate.

Development of the Ovary

• Cortical cords extend from the developing ovary's surface epithelium into the mesenchyme.
• These increase in size, breaking into cell clusters (primordial follicles).
• After birth, flattening of the surface epithelium to a single layer of cells occurs.
• The surface epithelium is separated from the follicles by the tunica albuginea, a thin fibrous capsule.
• The ovary is suspended by the mesovarium.

Duct Differentiation

• Mesonephric (Wolffian) ducts and paramesonephric (Müllerian) ducts develop parallel to each other.
• Paramesonephric ducts are funnel-shaped and open into the peritoneal cavity.
• Paramesonephric ducts cross ventrally to the mesonephric ducts and form a Y-shaped uterovaginal primordium.
• The uterovaginal primordium projects into the dorsal wall of the urogenital sinus, forming the sinus tubercle.

Female Reproductive Organs

• The paramesonephric ducts develop due to the absence of AMH.
• Oestrogens stimulate the development of the uterine tube, uterus, and superior part of the vagina.
• Uterine tubes develop from unfused cranial parts of the paramesonephric ducts.
• The uterovaginal primordium gives rise to the uterus and the superior part of the vagina.
• Mesonephric ducts fuse to form the uterovaginal primordium.
• The uterovaginal primordium projects into the dorsal wall of the urogenital sinus to give the sinus tubercle.
• Sinus tubercle induces the development of sinovaginal bulbs, forming the vaginal plate.
• The vaginal plate forms the vagina, with central cells breaking down to form the lumen, separated from the urogenital sinus by the hymen.
• Broad ligament fusion forms a peritoneal fold on either side.
• Forms the rectouterine and vesicouterine pouches.
• Paraurethral glands develop from urethral outgrowths, while greater vestibular glands develop from urogenital sinus outgrowths.

Male Ducts

• Testosterone stimulates the mesonephric duct's development and differentiation.
• Mesonephric tubules become the efferent ductules.
• Mesonephric duct's proximal part becomes the epididymis.
• Mesonephric duct becomes the vas deferens
• Lateral mesonephric duct outgrowths become the seminal vesicles at the caudal end.
• Prostate develops from the mesenchyme.

Abnormalities of the Uterus

• Double uterus (uterus didelphys) results from the failure of fusion of the inferior paramesonephric ducts, potentially with a double or single vagina.
• The uterus appears normal externally but is divided internally by a thin septum.
• Bicornuate uterus occurs when duplication involves only the superior part of the body.
• Bicornuate uterus with a rudimentary horn has a retarded paramesonephric duct that doesn't fuse with the second duct.
• Unicornuate uterus occurs when one paramesonephric duct fails to develop.
• A twin pregnancy in a bicornuate uterus can result in one fetus in each horn.

Abnormalities of the Vagina

• Absence of the Vagina- Failure of the sinovaginal bulbs to develop and form the vaginal plate.
• Rudimentary second Vagina.
• Partial Septate vagina.
• Atresia- Failure of canalization of the vaginal plate.
• Failure of the inferior end of the vaginal plate to perforate results in an imperforate hymen.

Remains of Embryonic Genital Ducts

• Some duct parts remain vestigial and can cause pathological issues.
• Examples in females include the epoophoron persisting in the mesovarium, Gartner duct cysts along the uterus, and a hydatid.
• The hydatid is (of Morgagni).
• Males- the cranial end of the mesonephric duct may persist as an appendix of the epididymis.
• The prostatic utricle persists.
• The prostatic utricle is the small sac-like structure.
• The prostatic utricle arises from the Paramesonephric duct.

External Genitalia - Males

• Masculinization of the indifferent external genitalia is induced by testosterone.
• The primordial phallus enlarges to form the penis.
• A urethral plate forms on the ventral side.
• The urethral plate becomes the urethral groove.
• The urethral folds fuse along the ventral surface of the penis to form the spongy urethra.
• The two labioscrotal swellings grow toward each other and fuse to form the scrotum.

External Genitalia - Females

• The primordial phallus gradually becomes the clitoris.
• Urethral folds do not fuse, except to form the frenulum.
• The unfused parts of the urogenital folds form the labia minora.
• The labioscrotal enlarges, forming labia majora.

Hypospadias

• A common defect is Hypospadias
• Results from inadequate androgen production or receptor sites for hormones.
• The penis is underdeveloped and curved.
• The external urethral orifice exists on the surface.
• Glans penis (glandular hypospadias)
• Body of the penis (penile hypospadias).
• Junction of the penis and scrotum (penoscrotal hypospadias)
• Scrotum (perineal hypospadias)

Epispadias

• The Urethra opens on the dorsal surface.
• Associated with the exstrophy of the urinary bladder.
• The urinary bladder opens broadly onto the abdominal wall.
• Results of ectodermal-mesenchymal interactions in the tubercle.

Urorectal Fistula

• The incomplete separation of the cloaca due to the septum.
• Meconium in urine (males)
• Meconium in vestibule (females).

Descent of the Gonads

• The gonads descend the gubernaculum towards the labioscrotal swellings.
• Males process vaginalis protrudes into the labioscrotal swellings.
• Processus vaginalis pushes through the abdominal wall.
• The female descends the gonad far as the pelvic cavity.
• During which the ovarian ligament remains as part of the gubernaculums and attaches to the ovary and uterus
• The round ligament is between the uterus and the labia.
• The testis acquires layers from the abdominal wall (skin, superficial fascia, external oblique and internal oblique).
• During which the processus extends out of the swelling that project in the scrotum and acquires layers of the testis (Skin, Colles Fascia and Dartos muscle , External cremasteric fascia-spermatic, internal spermatic).

Other abnormalities

• Cryptorchidism occurs where tests are hidden near the inguinal canal.
• Congenital ovarian hypoplasia syndrome or Tuerner's syndrome results in the absence of Oocytes
• Some male cells have both, ovum and tests leading to ovotestis
• 46, XX chromosomes have excessive production of hormones which can lead to abnormalities.