Development of female genital system Dr. Lubna Nazli

Objectives Devp of ovaries, uterus and fallopian tubes Devp of external genitalia Congenital malformations of FGS Hermaphrodites: types

The primordial germ cells arise from the yolk sac/endoderm and migrate into the intermediate mesoderm

Development of ovaries Is from the same source as the testis. The intermediate mesoderm/ genital ridge, is invaded by the sex cells arising from the yolk sac endoderm. These sex cells are having XX chromosomal complement, in absence of SRY gene, the anti-mullerian factor is not produced.

Migration of sex cells Along dorsal mesentery

The primary sex cords grows into the medulla. They give rise to secondary sex cords. Later they form the primordial ovarian follicles. The mullerian duct system develops parallel to the mesonephric duct.

The paramesonephric ducts are formed by infolding of the coelomic epithelium. Parallel to the mesonephric ducts, paramesonephric ducts grows/ Mullerian ducts.

Female fetus In the absence of TDF, medulla regresses and cortical sex cords break up into isolated cell clusters(primordial follicles) in the absence of AMH & testosterone, Mesonephric duct system degenerates Then, paramesonephric duct system develops Inf. fused portion Uterovaginal canal -> uterus and upper vagina Cranial unfused portions Open into celomic cavity(future peritoneal cavity) Fallopian tubes

The PMN duct form the fallopian tubes from the upper 1/3rd, fundus, body and cervix from the fused middle 1/3rd and lower 1/3rd will form the upper part of vagina.

The lower end of the duct opens up in the urogenital sinus/ the posterior wall of cloaca. The vagina develops from the sinovaginal bulb.

The female external genitalia development At the lower end of the embryo, around the cloacal membrane a median genital tubercle grows and it is called as phallus. On either side of the cloacal membrane, a labioscrotal swellings develop, the fore runner of the labia majora. In female fetus, the labioscrotal swelling will give rise to labia majora. The labia minora is developing from the urethral folds that has not united. The undeveloped phallus remains as clitoris.

The embryological derivatives Clitoris = median genital tubercle Labia majora = Labioscrotal swellings/lateral genital swellings Labia minora = Urethral groove Vagina = sinovaginal bulb Uterus/tubes = Paramesonephric ducts Ovary = Genital ridge/Intermediate mesoderm

Congenital anomalies of uterus development

Unicornuate - Where one of the Müllerian duct fails to develop resulting in a single uterine horn . Bicornuate - Both ducts form but one duct develops to a greater extent than the other. Consequently a small "rudimentary horn" exists, which may end blind or be continuous with the dominant horn. There is usually only one cervix.

Double vaginas Double - Complete failure of fusion of the Müllerian ducts. As a result of the independence of the ducts, two uteri develop, each with their own cervix. In addition one or two vaginas may be found. Septate - Both ducts develop but they only partially fuse. This leaves a septum at the fundus

Imperforate hymen If the cloacal membrane does not rupture It will give rise to imperforate hymen A congenital anomaly

Other Congenital Malformations Ovarian hypoplasia Pure gonadal dysgenesis Testicular feminization syndrome Hermaphroditism true Female pseudohermaphroditism Male pseudohermaphroditism

Pure Gonadal Dysgenesis Normal karyotypes (46, XX or 46, XY) Primordial germ cells do not migrate from the yolk sac No development of the ovaries or testes

Testicular Feminization Syndrome Occurs at rate of 1:50,000 Appears to be a normal female despite the presence of testes in either abdomen or inguinal region Testes produce normal levels of testosterone Tissues unresponsive to androgens External genitalia are normal Shallow blind ending vagina

Hermaphroditism True hermaphrodite Both ovaries and testicular tissue present Masculine form Feminine form Intermediate form (more common) 46, XX/ 46, XY or 46, XX/ 47, XXY

Hermaphroditism Female pseudohermaphroditism (46, XX) AKA congenital adrenogenital syndrome Masculinization due to high level of androgens from adrenal cortex Male pseudohermaphroditism Testes and ambiguous female genitalia Many types, most common is of unknown etiology Often considered females at a young age because penis is absent Raised as girls until puberty when male secondary sex characteristics appear via endocrine activities of testes

Genital system abnormalities Congenital defects in sexual development, usually arising from a variety of chromosomal abnormalities, tend to present clinically with ambiguous external genitalia Known as intersex conditions or hermaphroditism Classified according to the histologic appearance of the gonads

(1) True hermaphroditism Individuals with true hermaphroditism Have both ovarian and testicular tissue Most commonly as composite ovotestes Occasionally with an ovary on one side and a testis on the other In the latter case, a fallopian tube and single uterine horn may develop on the side with the ovary      ∵ absence of local AMH Extremely rare condition

(2) Pseudohermaphroditism In individuals with pseudohermaphroditism, Genetic sex indicates one gender External genitalia has characteristics of the other gender Caused either by abnormal levels of sex hormones or abnormalities in the sex hormone receptors

(2) Pseudohermaphroditism Males with pseudohermaphroditism Genetic males with feminized external genitalia Hypospadias(urethral opening on the ventral surface of the penis) Incomplete fusion of the urogenital or labioscrotal folds ; m/c manifesting sx. Females with pseudohermaphroditism Genetic females with virilized external genitalia Clitoral hypertrophy Some degree of fusion of the urogenital or labioscrotal folds