Embryology: Uterus, Cloaca and Genitalia

• This lecture discusses the embryology of the cloaca, uterus, and external genitalia.
• It also covers the development of the renal and genito-urinary systems.

Learning Outcomes

• Outline sex differentiation and gonadal development in male and female embryos.
• Explain the development of the paramesonephric duct and uterus in females, including potential abnormalities.
• Describe cloaca development into the urogenital sinus and rectum.
• Explain perineal development in both males and females, recognizing common abnormalities like hypospadias.
• Recognize common intersex states.

Indifferent Gonads

• Reproductive system development integrates with primitive urinary organs in both sexes.
• By the 6th week of development, the gonadal ridge forms.
• Primordial germ cells migrate from the yolk sac via the dorsal mesentery.
• These then populate the mesenchyme in the posterior body wall.
• A thickened mesothelium area develops on the mesonephros's medial side.
• The coelomic epithelium forms somatic support and interstitial stromal cells.
• Somatic support cells completely invest germ cells and are crucial for their development.
• Paramesonephric ducts, also known as Müllerian ducts, start forming lateral to the mesonephric ducts in both male and female embryos.
• Caudal ends of these ducts grow, adhere, and connect with the pelvic urethra, crossing ventral/anterior to the mesonephric ducts.
• Cranial ends form funnel-shaped openings into the peritoneal cavity.
• Germ and somatic support cells are in the presumptive gonads of both sexes, with mesonephric and paramesonephric ducts lying side by side.
• Genetic sex determination hinges on whether the sperm carries an X or a Y chromosome
• In XX embryos, the indifferent gonad's cortex differentiates into an ovary, and the medulla regresses.
• In XY embryos, the indifferent gonad's medulla differentiates into a testis, and the cortex regresses.

Male Sex Differentiation

• The Y chromosome's sex-determining gene produces a protein, the testis-determining factor.
• Gonadal cords differentiate into seminiferous cords, later tubules.
• Sex cords condense and penetrate the medulla.
• Some cells differentiate into Sertoli cells.
• Mesenchyme between the seminiferous cords differentiates into Leydig cells.
• Sertoli cells secrete antimüllerian hormone, causing the paramesonephric duct to degenerate.
• Leydig cells secrete testosterone.
• Testosterone is converted to dihydrotestosterone.
• This results in the differentiation of the mesonephric duct, prostate, and external genitalia.

Development of the Testis

• The sex-determining gene on the Y-chromosome produces a protein (testis-determining factor).
• This protein promotes testis development.
• Primitive sex cords proliferate and penetrate the medulla, forming testicular cords and seminiferous tubules.
• Leydig cells (from the mesenchyme) secrete testosterone, differentiating mesonephric ducts.
• Sertoli cells secrete AMH, causing regression of paramesonephric ducts.

Female Sex Differentiation

• Absence of the SRY gene results in female development.
• No Sertoli or Leydig cells are developed.
• The paramesonephric ducts differentiate and develop.
• Mesonephric ducts degenerate.

Development of the Ovary

• Cortical cords extend from the surface epithelium of the developing ovary into the mesenchyme.
• These cords increase in size, breaking up into primordial follicles.
• After birth, the surface epithelium of the ovary flattens into a single layer of cells.
• The surface epithelium separates from the follicles in the cortex via the tunica albuginea.
• As the ovary separates, it is suspended by the mesovarium.

Duct Differentiation

• The mesonephric duct is also known as the Wolffian duct
• The paramesonephric duct is also known as the Mullerian duct
• Paramesonephric ducts run parallel to the mesonephric ducts.
• Cranially, they are funnel-shaped and open into the peritoneal cavity.
• Caudally, they cross ventral to mesonephric ducts and fuse, forming the uterovaginal primordium.
• The uterovaginal primordium projects into the urogenital sinus’s dorsal wall, forming the sinus tubercle.

Female Reproductive Organs

• Paramesonephric ducts develop due to the absence of AMH.
• Oestrogens stimulate the development of the uterine tube, uterus, and the vagina's superior part.
• Uterine tubes develop from the unfused cranial parts of the paramesonephric ducts.
• The uterovaginal primordium creates the uterus and the superior section of the vagina.

Vagina and Broad Ligament

• Paramesonephric ducts fuse into the uterovaginal primordium.
• Uterovaginal primordium forms projection into the dorsal wall of the urogenital sinus to give the sinus tubercle.
• The sinus tubercle induces the development of the sinovaginal bulbs, which form the vaginal plate.
• The vaginal plate creates a vagina, the central cells here break down to form the lumen
• A membrane separates the vagina from the urogenital sinus, known as the hymen.
• Fusion forms a peritoneal fold, the broad ligament, creating the rectouterine and vesicouterine pouches.
• Paraurethral and greater vestibular glands form due to the outgrowths of the urethra and urogenital sinus.

Male Ducts

• Testosterone stimulates the development and differentiation of the mesonephric duct.
• Mesonephric tubules turn into efferent ductules.
• Proximal parts of the mesonephric duct become convoluted, becoming the epididymis.
• Mesonephric ducts become the vas deferens.
• Lateral outgrowths of the mesonephric duct's caudal end become the seminal vesicles.
• The urethra’s prostatic outgrowths will grow into the surrounding mesenchyme and become the prostate.

Abnormalities of the Uterus

• Double uterus (uterus didelphys) occurs due to the failure of the inferior parts of the paramesonephric ducts to fuse.
• It may or may not be associated with a double vagina.
• The uterus appears normal externally but is divided internally via a septum.
• If just the superior part of the uterus is affected, it's known as the bicornuate uterus.
• Bicornuate uterus with a rudimentary horn indicates that the growth of one paramesonephric duct has been affected and does not fuse with the second duct.
• Unicornuate uterus refers to just one paramesonephric duct developing.

Abnormalities of the Vagina

• Absence of the vagina results from the failure of the sinovaginal bulbs to develop and form the vaginal plate.
• This is usually with an absent uterus
• There can be Rudimentary second vaginas, partial septate vaginas, and atresia.
• Atresia result from the failure of canalization of the vaginal plate
• The inferior end of the vaginal plate may fail to perforate creating the imperforate hymen.

Remains of Embryonic Genital Ducts (Female)

• Epoophoron are nonfunctional blind tubules and a duct that may persist in the mesovarium between the ovary and uterine tube.
• Gartner duct cysts are parts of the mesonephric duct that may persist along the lateral wall of the uterus and in the wall of the vagina.
• A hydatid (of Morgagni) is part of the paramesonephric duct’s cranial end that can persist as a vesicular appendage,. These do not contribute to the infundibulum of the uterine tube.

Remains of Embryonic Genital Ducts (Male)

• The mesonephric duct's cranial end can still exist as an appendix of the epididymis.
• The prostatic utricle consists of a small sac-like structure arising from the paramesonephric duct.

External Genitalia (Male)

• Masculinization of the indifferent external genitalia is induced by testosterone.
• The primordial phallus elongates, forming the penis.
• A urethral plate forms ventrally on the phallus, resulting in a urethral groove.
• The urethral folds surround the groove that fuse to form the spongy urethra.
• The labioscrotal swellings grow toward each other eventually turning into the scrotum.

External Genitalia (Female)

• The primordial phallus gradually becomes the clitoris in females.
• The urethral folds do not fuse, except joining to create the frenulum of the labia minora.
• The unfused parts of the urogenital folds become the labia minora.
• The Labioscrotal folds don't fuse but do turn into the two distinct skin folds known as the labia majora.

Hypospadias

• Hypospadias is a common defect where the external urethral orifice is on the ventral surface.
• The penis underdeveloped and curved ventrally
• Results from inadequate testosterone and androgen production/reception.
• This ventral surface where the external urethral orifice is on can be on the Glans penis, body or junction of the penis, and the unfused halves of the scrotum.

Epispadias

• The urethra has an opening on the dorsal surface
• This is associated with bladder exstrophy, where the bladder isn't where it should be
• Comes from interactions that didn't develop adequately during the genital tubercle
• Tubercle here develops dorsally.

Urorectal Fistula

• The incomplete separation of the cloaca from the urogenital sinus (Urorectal septum) lead to this fistula.
• Meconium is present in the urine (in males) and the vestibule (in females).

Descent of the Gonads

• Descent of the Gonad refers to labioscrotal swellings that are being given guidance by the gubernaculum.
• In males, an outpouching protrudes to the labioscrocal, this is known as the processus vaginalis
• The processus vaginalis goes through the abdominal wall’s layers.
• In females, the descent goes just as far as the pelvic area
• In Ovarian Ligaments that are parts of the Gubernaculum the descent is limited to just the area between the ovary and the uterus.

Scrotum Layers

• Processus vaginalis is an extension/outpouching that projects into a labioscrotal swelling
• It usually disappears except that distal area
• As the testes move a certain layers from the abdominal wall will show up as well
• These layers include the skin, superficial area and external oblique.
• The layers in the body of the testicles include the skin, colle's fascia and external spermatic fascia.

Cryptorchidism

• Cryptorchid refers to testes that aren't in the right place, in this case those inside the inguinal canal or in the abdominal are
• Most undescended testes go to the scrum by the end of the first year.
• The testes also may not head through the inguinal canal which causes different issues.

Patent Processus Vaginalis

• Persistent processus vaginalis refers to cases where the tunica vaginalis between the peritoneum can’t fully close
• Peritoneal fluids pass through the Patent Processus Vaginalis
• This turn into a Scrotal Hydrocele
• When that central part in fact remains open there can be fluid accumulating which causes Hydrocele of the Spermatic cord

Congenital ovarian hypoplasia syndrome (Turner syndrome)

• The Karyotype is often 45,XO
• No Oocytes remain So the production of Hormones stop once your born
• As a result the areas around stay infantile with the syndrome’s characteristics.

Sex chromosome abnormalities

• 46,XX is referred to as excessive hormone in the adrenal.
• The Genitalia develop into a Male direction although there aren't Ovarian Abnormalities
• 46,XY have no hormone
• Any tissue unaffected gives way to the growth and development of the female.

Summary of Lecture

• Females:
  • Mesonephric duct disappears (mostly but does show up when the ureter needs to get to certain parts and when the gonads need certain help getting places) Those key things include The Ureteric bud and Epoophoron
  • Mesonephric ducts that remain have the Para, Fallopian tubes the Uterus and the upper part around one third of your Vagina
• Males
  • Mesonephric has the Wolffiam Area around and includes what are today’s gonads and also the Uterer. Where is today the duct is referred to as Wolves, you know the vas deferens
  • Only parts not in use are in the test. Prostatic and Appendix.