Reproductive Embryology

Reproductive Embryology By Ida HarrisSummary:Wk 5: primordial germ cells (from yolk sac) migrate into singular, undifferentiated gonad (located at T10)

Wk 6: undifferentiated genitaliain males, the medulla attaches to the mesonephric ductsTESTESIn females, the cortex attaches to the paramesonephric ductsOVARY In both sexes, the cloaca septates into the bladder and rectumThe metanephros (future kidney) buds from the mesonephric duct

Wk 7: both Mullerian and Wolffian ducts are present

Wk 10: Recognizable genitalia

Intermediate MesodermBecomes the suprarenal glands, gonads, kidneys and associated tubes and vasculatureOverview- MaleThe male reproductive tract forms from Wolffian ductsSeminal VesiclesEpidydimisEjaculatory DuctDuctus Deferens

Both the gonads and the Wolffian ducts form from intermediate mesoderm

The Wolffian duct forms from the mesonephric duct(from intermediate mesoderm), left over from the mesonephros (at wk 12).

Intermediate mesoderm also forms the gubernaculum, which pulls the testes down into the scrotum

Overview: Male IIAt wk 5, the gonads receive primordial germ cells from the yolk sac

At wk 6, the medulla of the undifferentiated gonad attaches to the mesonephric ducts above the metanephros and becomes the testes.This is induced by testosterone, stimulated by the SRY gene on the Y chromosome.Stimulates Sertoli cells to secrete Mullerian inhibiting factorStimulates the growth of the Wolffian ducts

By week 7, both mullerian and Wolffian ducts are still present, but testosterone and MIF are actively produced

Descent of the testes is stalled at the inguinal ring until close to delivery time

Overview: Male IIIDHT (produced via 5-alpha reductase) induces external male genitalia differentiation (penis, scrotum)

SRY, Sox9 (gonads), AMH/MIF(ducts) gene expression

5-alpha reductase deficiency: lack of DHT prevents male differentiation until puberty (female external genitalia changes to penis at puberty)Overview: Male 2nd Sex Char.Testicular AndrogensExternal genitalia developmentFacial hairAxillary and pubic hairEnlargement of laryngeal cartilageand deepening of the voiceIncreased muscle mass

GH (adenohypophysis)Broadening of shouldersIncreased muscle mass

EstrogenGrowth spurt: estrogen receptors in bone

Overview-FemaleThe female reproductive tract forms from the Mullerian duct and the gonads, which are both formed from intermediate mesoderm

The Mullerian duct does NOT form from the mesonephric duct, rather it forms from the paramesonephric ducts into the fallopian/uterine tubes.

The Mullerian ducts fuse at the caudal end to form the uterus and top 1/3 of the vagina, remaining unfused at the other ends to form the fallopian tubes which end near the gonads/ovaries. Remnants also form the broad ligament, which suspends the ovaries in the abdominal cavityOverview: Female IIX chromosomes onlyStimulates Mullerian duct growth

Dax, Wnt4Dax inhibits Sox9 (gonads), SRY expression in XXY

Overview: Female 2nd Sex Char.Ovarian estrogenBreast developmentGenital developmentIncreased body fat and characteristic depositionGrowth spurt: estrogen receptors in bone

Progesterone (after menarche)Breast development

Ovarian/Adrenal androgensAxillary and pubic hair

GH (adenohypophysis)Increased hip width

Kidney Development

Intermediate MesodermBecomes the suprarenal glands, gonads, kidneys and associated tubes and vasculatureTimelineDay 18: intermediate mesoderm forms

Day 24:nephrogenic cord forms from intermediate mesoderm

Day 26:urogenital ridge (intermediate mesoderm) surrounds nephrogenic cords

Day 28+ (pronephros) forms from cranial nephrogenic cords

Day 28+ (wk4) to Day 84 (week12)(meSonephros) forms from middle nephrogenic cords

Day 42- (wk6)meTanephros forms from caudal mesonephric ductsAt this time, sexual differentiation is also occuring

Day 42 to 49 (wk6-7) cloaca(endoderm) separates to form rectum and bladder

Day 112 (wk 16) metanephros has lobes and function as the collecting ducts and ureter of the final kidney. The metanephric blastema becomes the nephrons.

Timeline II-kidneyWk 40ConceptionPronephros, wk 4, degenerates after a few days, useless Mesonephros (S for second) wk 4 to wk12, connects to blood vessels at wk 6-7 to function as rudimentary kidneyMetanephros (T for third), wk 6 onwards, buds out from mesonephric duct, inducing the mesoderm around it (metanephrogenic blastema) to become kidney renal tubules (nephrons) while it becomes the ureter, renal pelvis, calyxes and collecting duct system of the kidney.Timeline III- with bladderWk 40ConceptionPronephros(wk4)Mesonephros wk 4 to wk12Metanephros wk 6 onwardsCloaca (endoderm)Hindgut separates into rectum (by wk7)

Bladder (by wk 7)

Kidneys intermediate mesoderm

Know the Nephros

First, useless kidney, formed and disintegrated at week 4Part of mesonephros; the second, transitory kidney (wk4) Joins with gonad medulla in males to become the male reproductive tract (wk6). Third, final kidney, formed at week 6 The migrations of kidneys/gonads

Kidneys go up/Gonads go downKidneys trade up for new arteries/Gonads take their arteries down with them.Testes descend to the deep inguinal ring in week 12At month 7-9, testes continue to descend into the scrotumAdrenal/Epinephrine glandsCortex forms from intermediate mesoderm of the abdomen

Medulla forms from migratory neural crest sympathetic gangliaChromaffin cells

Developmental AnomaliesMale Developmental AnomaliesHypospadius: urethra opens on the underside/inferior side of the penis instead of through the center of the glans.Can be panscrotal, penile or in the glans.

Epispadius: urethra opens on the superior side of the penis instead of through the glans.

Cryptoorchidism: Failure of the testes to descend into the scrotumAssociated with persistent Mullerian duct syndrome

Testicular hydrocele: fluid filled cysts in the scrotum

Indirect Inguinal HerniaMDs dont Lie (Indirect Inguinal hernias happen to infants and are lateral to the inguinal ring) (medial:direct)Female Developmental AnomaliesFrom not enough joining to too much:Double uterus and vaginaDouble uterus

Bicornate uterusSeptated uterus

NORMAL uterusCervical atresia

Other: unicornate uterus

If only one Mullerian duct is presentNot enough fusion of the Mullerian ductsToo much fusion of the Mullerian ductsExternal GenitaliaExternal Genitalia IGenital tubercleMale- glans penis and corpus cavernosumFemale- glans clitoris and clitoral crura and shaft

Urogenital SinusMale , bulbourethral glands of Cowper, prostate glandFemale-, greater vestibular glands of Bartholin, urethral and Skenes (paraurethral) glandsAlso forms the urethra, bladder and allantois

Urogenital FoldsMale- ventral shaft of penis, corpus spongiosumFemale-labia minora, vesticular bulbs

Labioscrotal FoldsMale-scrotumFemale-labia majora

Urogenital FoldGenital TubercleLabioscrotal swellingIndifferent State (male=female)Primordial PhallusAnal MembraneUrogenital membraneUrogenital FoldLabioscrotal swelling

Cloacal Membrane Becomes the ventral shaft of penis (corpus spongiosum) in malesBecomes the labia minora and vestibular bulbs in females Becomes the glans penis and corpus cavernosum in malesBecomes the glans clitoris, crura and shaft of the clitoris in femalesBecomes the scrotum in malesBecomes the labia majora in females

MaleFemaleUrogenital folds fuse to become the corpus spongiosum of the penile shaft, the labioscrotal folds fuse to become the scrotum. The genital tubercle sticks out at the end of the penis as the glans penis. The rest of the genital tubercle fuses with the urogenital folds to become the corpus cavernosum. External Genitalia IIMaleInduced by DHTSynthesis of DHT requires 5-alpha reductase

Female: lack of DHTSummary:Wk 5: primordial germ cells (from yolk sac) migrate into singular, undifferentiated gonad

Wk 6: undifferentiated genitaliain males, the medulla attaches to the mesonephric ductsTESTESIn females, the cortex attaches to the paramesonephric ductsOVARY In both sexes, the cloaca septates into the bladder and rectumThe metanephros (future kidney) buds from the mesonephric duct

Wk 7: both Mullerian and Wolffian ducts are presentY (SRY) chromosome induces testosteronestimulates testes formation (making more testosterone/positive feedback)Stimulates Sertoli cells to secrete Mullerian inhibiting factorStimulates the growth of the Wolffian ductsX chromosomes onlyStimulates Mullerian duct growth

Wk 10: External Genitalia: DHT/5-aR for male differentiation (female default)

QuizWhere do primordial germ cells come from?Yolk sac

When do they invade the undifferentiated gonad?Wk 5

What happens to the undifferentiated gonad in males?Medulla joins with mesonephric duct

In females?Cortex joins with paramesonephric duct

Quiz IIWhat forms from intermediate mesoderm?Gonads, Wolffian/Mullerian ductsUpper 1/3 of vagina, uterus, fallopian tubes, ovaries, broad ligamentTestes, Seminal Vesicles, Epidydimis, Ejaculatory Duct, Ductus Deferens, GubernaculumBasically everything except external genitalia

Adrenal glands, kidneysAssociated vasculature

Quiz IIIWhat are the undifferentiated precursors of external genitalia? (and the prostate which is internal)Genital tubercle- glans penis/clitoris, crura and shaft of the clitoris, corpus cavernosum of the penis

Urogenital Sinus- bulbourethral glands of Cowper, prostate gland in the male, greater vestibular glands of Bartholin, urethral and Skenes (paraurethral) glands in the female. Also develops into the bladder, urethra and allantois.

Urogenital Folds- ventral shaft of penis, corpus spongiosum ,labia minora, vesticular bulbs

Labioscrotal folds- labia majora, scrotum

What do they become?

Quiz IIIWhat genes cause male gonadal differentiation?SRY, Sox9

What allow Wolffian duct proliferation?Testosterone, MIF/AMH

What causes male external genitalia differentiation?DHT, requiring 5-alpha reductase

What genes cause female gonadal differentiation?Dax inhibits Sox9, absence of SRY

What causes female external genitalia differentiation?Lack of DHT

BibliographyClass NotesPodcastFirst AidWikipedia