Reproductive Embryology By Ida Harris Summary Wk 5

Reproductive Embryology By Ida Harris

Summary: �Wk 5: primordial germ cells (from yolk sac) migrate into singular, undifferentiated gonad (located at T 10) �Wk 6: undifferentiated genitalia � in males, the medulla attaches to the mesonephric ducts TESTES � In females, the cortex attaches to the paramesonephric ducts OVARY � In both sexes, the cloaca septates into the bladder and rectum � The metanephros (future kidney) buds from the mesonephric duct �Wk 7: both Mullerian and Wolffian ducts are present �Wk 10: Recognizable genitalia

Intermediate Mesoderm Becomes the suprarenal glands, gonads, kidneys and associated tubes and vasculature

Overview- Male � The male reproductive tract forms from Wolffian ducts � Seminal Vesicles � Epidydimis � Ejaculatory Duct � Ductus 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 II � At 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 factor � Stimulates 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 III �DHT (produced via 5 -alpha reductase) induces external male genitalia differentiation (penis, scrotum) �SRY, Sox 9 (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 nd 2 Sex Char. � Testicular Androgens � External genitalia development � Facial hair � Axillary and pubic hair � Enlargement of laryngeal cartilageand deepening of the voice � Increased muscle mass � GH (adenohypophysis) � Broadening of shoulders � Increased muscle mass � Estrogen � Growth spurt: estrogen receptors in bone

Overview-Female �The 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 cavity

Overview: Female II �X chromosomes only �Stimulates Mullerian duct growth �Dax, Wnt 4 �Dax inhibits Sox 9 (gonads), SRY expression in XXY

Overview: Female nd 2 Sex Char. � Ovarian estrogen � Breast development � Genital development � Increased body fat and characteristic deposition � Growth spurt: estrogen receptors in bone � Progesterone (after menarche) � Breast development � Ovarian/Adrenal androgens � Axillary and pubic hair � GH (adenohypophysis) � Increased hip width

Kidney Development

Intermediate Mesoderm Becomes the suprarenal glands, gonads, kidneys and associated tubes and vasculature

Timeline � Day 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+ (wk 4) to Day 84 (week 12)(me. Sonephros) forms from middle nephrogenic cords � Day 42 - (wk 6)me. Tanephros forms from caudal mesonephric ducts � At this time, sexual differentiation is also occuring � Day 42 to 49 (wk 6 -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-kidney Wk 40 Conception Pronephros, wk 4, degenerates after a few days, useless Mesonephros (S for second) wk 4 to wk 12, connects to blood vessels at wk 6 -7 to function as rudimentary kidney Metanephros (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 bladder Wk 40 Conception Pronephros(wk 4) Kidneys –intermediate mesoderm Mesonephros wk 4 to wk 12 Metanephros wk 6 onwards Hindgut separates into rectum (by wk 7) Cloaca (endoderm) Bladder (by wk 7)

Third, final kidney, formed at week 6 Know the ‘Nephros First, useless kidney, formed and disintegrated at week 4 Part of mesonephros; the second, transitory kidney (wk 4) Joins with gonad medulla in males to become the male reproductive tract (wk 6).

The migrations of kidneys/gonads Kidneys go up/Gonads go down Kidneys trade up for new arteries/Gonads take their arteries down with them. Testes descend to the deep inguinal ring in week 12 At month 7 -9, testes continue to descend into the scrotum

Adrenal/Epinephrine glands �Cortex forms from intermediate mesoderm of the abdomen �Medulla forms from migratory neural crest sympathetic ganglia �Chromaffin cells

Developmental Anomalies

Male Developmental Anomalies � Hypospadius: 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 scrotum � Associated with persistent Mullerian duct syndrome � Testicular hydrocele: fluid filled cysts in the scrotum � Indirect Inguinal Hernia � MDs don’t Lie (Indirect Inguinal hernias happen to infants and are lateral to the inguinal ring) (medial: direct)

Female Developmental Anomalies � From not enough joining to too much: � Double uterus and vagina � Bicornate uterus Double uterus Septated uterus Too much fusion of the Not enough fusion If of only the Mullerian one Mullerian ductsduct is present Mullerian ducts � NORMAL uterus � Other: unicornate uterus Cervical atresia

External Genitalia

External Genitalia I � Genital tubercle � Male- glans penis and corpus cavernosum � Female- glans clitoris and clitoral crura and shaft � Urogenital Sinus � Male –, bulbourethral glands of Cowper, prostate gland � Female-, greater vestibular glands of Bartholin, urethral and Skene’s (paraurethral) glands � Also forms the urethra, bladder and allantois � Urogenital Folds � Male- ventral shaft of penis, corpus spongiosum � Female-labia minora, vesticular bulbs � Labioscrotal Folds � Male-scrotum � Female-labia majora

Urogenital Fold Becomes the ventral shaft of penis (corpus spongiosum) in males Labioscrotal swelling Becomes the labia minora and vestibular bulbs in females Primordial Phallus Urogenital Fold Genital Tubercle Becomes the glans penis and corpus cavernosum in males Becomes the glans clitoris, crura Cloacal Membrane and shaft of the clitoris in females Indifferent State (male=female) Urogenital membrane Labioscrotal swelling Becomes the scrotum in males Becomes the labia majora in females Anal Membrane

Male Urogenital 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. Female

External Genitalia II �Male �Induced by DHT �Synthesis of DHT requires 5 -alpha reductase �Female: lack of DHT

Summary: � Wk 5: primordial germ cells (from yolk sac) migrate into singular, undifferentiated gonad � Wk 6: undifferentiated genitalia � in males, the medulla attaches to the mesonephric ducts TESTES � In females, the cortex attaches to the paramesonephric ducts OVARY � In both sexes, the cloaca septates into the bladder and rectum � The metanephros (future kidney) buds from the mesonephric duct � Wk 7: both Mullerian and Wolffian ducts are present � Y (SRY) chromosome induces testosterone � � � stimulates testes formation (making more testosterone/positive feedback) Stimulates Sertoli cells to secrete Mullerian inhibiting factor Stimulates the growth of the Wolffian ducts � X chromosomes only � Stimulates Mullerian duct growth � Wk 10: External Genitalia: DHT/5 -a. R for male differentiation (female default)

Quiz �Where 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 II �What forms from intermediate mesoderm? �Gonads, Wolffian/Mullerian ducts � Upper 1/3 of vagina, uterus, fallopian tubes, ovaries, broad ligament � Testes, Seminal Vesicles, Epidydimis, Ejaculatory Duct, Ductus Deferens, Gubernaculum � Basically everything except external genitalia �Adrenal glands, kidneys �Associated vasculature

Quiz III � What 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 Skene’s (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 III � What genes cause male gonadal differentiation? � SRY, Sox 9 � 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 Sox 9, absence of SRY � What causes female external genitalia differentiation? � Lack of DHT

Bibliography �Class Notes �Podcast �First Aid �Wikipedia