Chapter 1 - Female Genital Tract Development and Disorders of Childhood

Abstract

Female reproductive tract development is a complex process intricately tied to the patterning of the male (Wolffian) reproductive tract and renal anlage. Development starts from undifferentiated mesoderm known as the genital ridge, with germ cells migrating to this location from the yolk sac. The müllerian duct begins as an invagination of the coelomic epithelium at the top of the genital ridge and elongates by active cell proliferation using the Wolffian duct as a guide. Many genes have been linked to female reproductive tract development, but only a few have been directly implicated by animal knockout models; this is because the simplex female reproductive tract pattern (i.e., one with a single cervix and uterus, with two separate fallopian tubes) is limited to humans and other primates. Most recently, genomic sequencing has identified more genes, mostly transcription factors and extracellular signaling molecules, and mutations in those genes, associated with malformations of the female reproductive tract. The most common congenital abnormality of the human female genital tract occurs when the paired müllerian ducts fail to fuse or the subsequent septum fails to resorb, yielding a spectrum of uterine anomalies, including uterus didelphys and bicornuate uterus. External female genital tract development requires both the absence of a key male determining factor (SRY) and presence of its antagonist (WNT4). Virilization of genetically female fetuses is due to excessive androgens from congenital adrenal hyperplasia or maternal blood.