DEVELOPMENT OF FEMALE GENITAL SYSTEM By: Dr. Mujahid Khan

Development of Gonads The gonads are derived from 3 sources: The gonads are derived from 3 sources:  The mesothelium (mesodermal epithelium) lining the posterior abdominal wall  The underlying mesenchyme (embryonic connective tissue)  The primordial germ cells

Indifferent Gonads  The initial stages of gonadal development occur during the fifth week  A thickened area of mesothelium develops on the medial side of the mesonephros  Proliferation of this epithelium and the underlying mesenchyme produces a bulge on the medial side of the mesonephros called gonadal ridge

Indifferent Gonads  Finger like epithelial cords or Gonadal cords soon grow into the underlying mesenchyme  The indifferent gonad now consists of an external cortex and an internal medulla  In embryos with an XX sex chromosome complex, the cortex differentiates into an ovary and the medulla regresses  In embryos with an XY sex chromosome complex, the medulla differentiates into a testis and the cortex regresses

Primordial Germ Cells  These large, spherical cells are visible early in the fourth week among the endodermal cells of the yolk sac near the allantois  During folding of the embryo, the dorsal part of the yolk sac is incorporated into the embryo  With this the primordial germ cells migrate along the dorsal mesentery of the hindgut to the gonadal ridges  During the sixth week the primordial germ cells enter the underlying mesenchyme and are incorporated in the gonadal cords

Sex Determination  Chromosomal and genetic sex is determined at fertilization  It depends upon whether an X-bearing sperm or a Y-bearing sperm fertilizes the X-bearing ovum  The type of gonads develop is determined by the sex chromosome complex of the embryo (XX or XY)

Sex Determination  Before the seventh week, the gonads of the two sexes are identical in appearance called indifferent gonads  Development of the male phenotype requires a Y chromosome  The SRY gene for a testes-determining factor (TDF) has been localized in the sex-determining region of the Y chromosome  Two X chromosomes are required for the development of the female phenotype

Sex Determination  The Y chromosome has a testes-determining effect on the medulla of the indifferent gonad  The absence of a Y chromosome results in the formation of an ovary  Testosterone, produced by the fetal testes, determines the maleness  Primary female sexual differentiation in the fetus does not depend on hormones  It occurs even if the ovaries are absent

Development of Ovaries  Gonadal development occurs slowly in female embryos  The X chromosomes bear genes for ovarian development and an autosomal gene also appears to play a role in ovarian organogenesis  The ovary is not identifiable histologically until about the 10 th week

Development of Ovaries  Gonadal cords do not become prominent but they extend into the medulla and form a rudimentary rete ovarii  This structure and gonadal cords normally degenerate and disappear  Cortical cords extend from the surface epithelium of the developing ovary into the underlying mesenchyme during the early fetal period

Development of Ovaries  As the cortical cords increase in size, primordial germ cells are incorporated in them  At about 16 weeks these cords begin to break up into isolated cell clusters called primordial follicles  Each primordial follicle consists of an oogonium, derived from primordial germ cell

Development of Ovaries  Each oogonium is surrounded by a single layer of flattened follicular cells derived from the surface epithelium  Active mitosis of oogonia occurs during fetal life producing thousands of primordial follicles  No oogonia form postnatally  Many oogonia degenerate before birth  About 2 million remain enlarge to become primary oocytes before birth

Development of Ovaries  After birth the surface epithelium of the ovary flattens to a single layer of cells continuous with the mesothelium of the peritoneum at the hilum of the ovary  The surface epithelium of the ovary was formerly inappropriately called the germinal epithelium  The surface epithelium becomes separated from the follicles in the cortex by a thin fibrous capsule called tunica albuginea  As the ovary separates from the regressing mesonephros, it is suspended by a mesentery called mesovarium

Development of Genital Ducts  Both male and female embryos have two pairs of genital ducts  The mesonephric ducts (wolffian ducts) play an important role in the development of the male reproductive system  The paramesonephric ducts (mullerian ducts) have a leading role in the development of the female reproductive system  Till the end of sixth week, the genital system is in an indifferent state, when both pairs of genital ducts are present

Development of Genital Ducts  The mesonephric ducts, which drained urine from the mesonephric kidneys play a major role in the development of male reproductive system  The paramesonephric ducts play an essential role in the development of the female reproductive system  The funnel shaped cranial ends of these ducts open into the peritoneal cavity  The paramesonephric ducts pass caudally, parallel to the mesonephric ducts

Development of Genital Ducts  Both the paramesonephric ducts pass caudally and reach the future pelvic region  Cross ventral to the mesonephric ducts  Fuse to form a Y-shaped uterovaginal primordium in the midline  This tubular structure projects into the dorsal wall of the urogenital sinus and produces an elevation called sinus (muller) tubercle

Development of Female Genital Ducts & Glands  In female embryos, the mesonephric ducts regress because of the absence of testosterone  Paramesonephric ducts develop because of the absence of mullerian inhibiting substance (MIS)  Female sexual development does not depend on the presence of ovaries or hormones  The paramesonephric ducts form most of the female genital tract

Development of Female Genital Ducts & Glands  The uterine tubes develop from the unfused cranial part of the paramesonephric ducts  The caudal fused portions of these ducts form the uterovaginal primordium  It gives rise to uterus and superior part of vagina  The endometrial stroma and myometrium are derived from splanchnic mesenchyme

Development of Female Genital Ducts & Glands  Fusion of the paramesonephric ducts also brings together a peritoneal fold that forms the broad ligament  Also forms two peritoneal compartments, the rectouterine pouch and the vesicouterine pouch

Development of Vagina  The vaginal epithelium is derived from the endoderm of the urogenital sinus  The fibromuscular wall of the vagina develops from the surrounding mesenchyme  Contact of the uterovaginal primordium with the urogenital sinus forming the sinus tubercle

Development of Vagina  Sinus tubercle induces the formation of paired endodermal outgrowths called sinovaginal bulbs  The sinovaginal bulbs fuse to form a vaginal plate  Later the central cells of the plate break down, forming lumen of vagina  The peripheral cells of the plate form the vaginal epithelium

Development of Vagina  Until the fetal life, the lumen of the vagina is separated from the cavity of the urogenital sinus by a hymen  The hymen is formed by invagination of the posterior wall of the urogenital sinus, resulting from expansion of the caudal end of the vagina  The hymen remains as a thin fold of mucous membrane just within the vaginal orifice

Development of External Genitalia  Up to the seventh week of development the external genitalia are similar in both sexes  Distinguishing sexual characteristics begin to appear during the ninth week  External genitalia are not fully differentiated until the twelfth week

Development of External Genitalia  Early in the fourth week, proliferating mesenchyme produces a genital tubercle in both sexes at the cranial end of the cloacal membrane  Labioscrotal swelling and urogenital folds soon develop on each side of the cloacal membrane  The genital tubercle soon elongates to form a primordial phallus

Development of External Genitalia  When the urorectal septum fuses with the cloacal membrane, it divides it into a dorsal anal membrane and a ventral urogenital membrane  The urogenital membrane lies in the floor of a median cleft, the urogenital groove, which is bounded by urogenital folds

Development of External Genitalia  The anal and urogenital membranes rupture a week later forming the anus and urogenital orifice, respectively  In female fetus the urethra and vagina open into a common cavity called vestibule

Development of Female External Genitalia  Estrogen produced by the placenta and fetal ovaries appear to be involved in feminization of indifferent external genitalia  Growth of the primordial phallus gradually ceases and becomes clitoris  The clitoris is relatively large at 18 weeks  It develops like a penis but the urogenital folds do not fuse, except posteriorly

Development of Female External Genitalia  Urogenital folds fuses posteriorly to form the frenulum of the labia minora  The unfused parts of the urogenital folds form the labia minora  The labioscrotal folds fuse posteriorly to form the posterior labial commisure

Development of Female External Genitalia  The labioscrotal folds fuse anteriorly to form the anterior labial commisure and mons pubis  Most parts of the labioscrotal folds remain unfused and form two large folds of skin called labia majora  Labia majora are homologous to the scrotum