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Development of Female Genital System Development of Female Genital System Gonads Genital Ducts Indifferent stage of sexual Indifferent

stage development Female genital ducts, Auxiliary genital glands Primordial germ cells Sex determination Development of Gonads (Testis & Ovaries) Mesodermal epithelium (mesothelium) Underlying mesenchyme Primordial germ cells Indifferent Gonads Primordial Germ Cells Origin - Endodermal cells of yolk sac (near origin of allantois) th During folding of embryo (5 week) y Dorsal part of yolk sac is incorporated into embryo y Primary germ cells migrate by amoeboid movement via dorsal mesentery of hindgut to gonadal ridges 6th week y Invade gonadal ridge y Incorporated into primary sex cords y Form oogonia

Influence of Primordial Germ Cells on Indifferent Gonad

Indifferent Gonads Gonadal ridge At 5th week, before & during arrival of germ cells Proliferation of underlying mesenchyme (from medial side of mesonephros) Proliferation of mesodermal epithelium lining posterior abdominal wall y Penetrate underlying mesenchyme y Form primary sex cords Produce bulge called gonadal ridge Indifferent Gonads Primary Sex Cords Connected to surface epithelium Cannot differentiate between male, female Indifferent gonads stage before 7 th week

Consists of y Outer cotex y Inner medulla Sex Chromosome XX Cortex differentiates into ovary Medulla regresses

XY Medulla differentiates into testis Cortex regresses

Effects of Primordial Germ Cells on Indifferent Gonad

Development of Genital Ducts Initially both ducts are present Female Paramesonephric duct (lateral) (Mullerian duct)

Male Mesonephric duct (medial)

Indifferent Stage Stage when both pairs of genital ducts are present Paramesonephric Ducts (Mullerian Duct) Origin Intermediate mesoderm Develop from longitudinal invagination of mesodermal epithelium Located lateral to mesonephric duct Caudally cross ventral to mesonephric duct, fused to form uterovaginal primordium/ canal Development of Genital Ducts, Auxiliary Genital Glands Female sexual development does not depend on presence of ovaries Cranial form uterine tubes Caudal uterovaginal primordium/ canal (form uterus, vagina (superior part)) Endometrial stroma, myometrium are derived from mesenchyme Fused paramesonephric duct form y Broad ligaments y Rectouterine pouch y Vesicouterine pouch Adjacent mesenchyme form parametrium Development of Vagina Derived from endoderm of urogenital sinus Fibromuscular wall is derived from mesenchyme Contact of uterovaginal primordial with urogenital sinus y Induces formation of paired endodermal outgrowths y Called sinovaginal bulbs Sinovaginal bulbs fused, form solid vaginal plate (later canalised) Cavity of urogenital sinus is separated by lumen of vagina (by hymen) Both surfaces are lined by endoderm Hymen rupture at perinatal period

Y chromosome has strong testis-determining effect Androgen testosterone produced by testis determines maleness Development of Ovaries Primitive Sex Cords Do not become prominent in female embryo (Male Seminiferous tubules) Extended into medulla, form rete ovarii Rete ovarii, primary sex cords normally disappear Secondary Sex Cords (Cortical Cords) Extends from surface epithelium (mesodermal epithelium) into underlying mesenchyme Primordial germ cells later incorporated into them forming oogonium th At 16 week, cortical cords break up into cell clusters called primordial follicles (oogonium + follicular cells) No oogonium form postnatally Primordial follicles form primary follicles

Differentiation of Internal Reproductive Tract

Development of Auxiliary Genital Glands Bud grow from urethra into mesenchyme, form urethral & paraurethral glands (of Skene) Outgrowth from urogenital sinus form greater vestibular glands Remnants in Females Mesonephric Appendix vesiculosa (cranial end) Epoophoron in broad ligament between ovary, uterine tube (correspond to efferent ductules, duct of epidydimis) Paroophron (rudimentary tubules near uterus) Duct of Gartner (correspond to ductus deferens, ejaculatory duct) Gartner s duct cysts (remnants of mesonephric duct)

Paramesonephric Vesicular appendages (cranial end of duct hydatid of Morgagni)

Auxiliary Genital Glands Outgrowths from y Uretrha paraurethral glands (of Skene) y UG sinus greater vestibular glands (of Bartholin) Paramesonephric remnants hydatid of Morgagni Mesonephric remnants y Epoophoron y Paroophoron y Gartner s cyst

Development of External Genitalia (Indifferent Stage) Distinguishing external genital organs fully differentiate at 12th week th At 4 week, a genital tubercle develops at cranial end of cloacal membrane Form on each side of cloacal membrane y Labioscrotal swellings (lateral) y Urogenital folds (medial) Genital tubercle elongates to form phallus

Development of External Genitalia Growth of phallus decreases (become clitoris) Urogenital folds only fuse posteriorly, form frenulum of labia minora Unfused part of urogenital folds form labia minora Labioscrotal folds (mostly remain unfused) to form labia majora Labioscrotal folds fuse Posteriorly Anteriorly Posterior labial commissure Anterior labial commissure Mons pubis Phallic part of urogenital sinus form the vestibule of vagina

Urorectal septum fuses with cloacal membrane, clocal membrane divided to y Anal membrane (dorsal) y Urogenital membrane (ventral) Urogenital membrane lies at floor of a median cleft (called urogenital groove) (bounded by urogenital folds) Urogenital membrane ruptures to form anus, urogenital orifice

Formation Urogenital/ genital folds Labioscrotal/ genital swellings Genital tubercle Urogenital groove

Labia minora Labia majora, Mons pubis Clitoris Vestibule

Descent of Ovary From lumbar region to true pelvis Gubernaculum (genital ligament) (extends from ovary to labia majora) Round ligament of ovary = ovarian ligament

Differences 6 Weeks Upper, lower gubernaculums in an embryo in the indifferent stage 4 Months Ovarian ligament, suspensory ligament of ovaries

Urorectal Septum Cloaca Primitive urogenital Anorectal canal

Cloacal Membrane Urogenital membrane Anal membrane

Cloacal Folds Urogenital folds Anal folds

Primitive Urogenital Sinus Urinary bladder Pelvic part Phallic part (definitive urogenital sinus)

Congenital Malformation of Female Genital System Congenital Anomalies of Female Genital System Female Pseudohermaphrodites 44 + XX chromosome complement Most common cause adrenogenital syndrome Ovaries present Androgen production Masculinization y Clitoral hypertrophy y Partial fusion of labia majora y Persistent urogenital sinus Conditions Related to Intersexuality Testicular Feminization Appear as normal females Present of testis XY sex chromosomes External genitalia Females y Vagina ends blindly y Uterus, uterine tubes absent Testis in inguinal/ labial regioins y At puberty y Normal development of breasts y Normal development of female characteristics No menstruation Pubic hair scanty

Male Pseudohermaphrodites 44 + XY chromosome complement Cause inadequate androgen production Have testis Internal, external characteristics Degree of phallus development Presence of paramesonephric duct

True Hermaphrodites Extremely rare Most are reared as female Physical appearance masculine/ feminine External genitalia - ambiguous

Gonadal Dysgenesis (Turner s Syndrome) 44 autosome XO chromosome External genitalia normal Sex characteristics remain infantile Primordial germ cells present No/ few true follicles develop Primordial germ cells migrate into gonadal area

Pure Gonadal Dysgenesis 44, XX or 44, XY Primordial germ cells do not form Primordial germ cells do not migrate to gonadal area Ovary/ testis do not develop

Malformation of Uterus, Vagina Causes of Malformation Incomplete fusion of paramesonephric ducts Incomplete development of one paramesonephric duct Failure of parts of one/ both paramesonephric ducts to develop Incomplete canalization of vaginal plate Uterus Uterus didelphys Uterus entirely double Failure of fusion of inferior parts of paramesonephric ducts Arcuate uterus Fundus is slightly indented in middle Septate uterus A septum divides the uterine cavity into 2 parts Bicornis bicollis Double uterus Double cervix Single vagina Unicornuate uterus Unilateral suppression of a paramesonephric duct Vagina Double vagina Sinovaginal bulbs fail to fuse Atresia of vagina Sinovaginal bulbs fail to develop Vesico-vaginal fistula Paramesonephric duct ruptures into vesico-urethral part of cloaca Abnormal communication with urinary bladder Recto-vaginal fistula Paramesonephric duct projects into rectal segment of cloaca Associated with incomplete development of urorectal septum