Chapter 27 - Development of the Genital System

Abstract

In mammals, sex determination is accomplished by a chromosomal mechanism. It begins at the time of fertilization through the coupling of two gametes: either two X chromosomes (XX in females) or an X and a Y chromosome (XY in males). The SRY gene is the sex determination gene of the Y chromosome. Gonadal differentiation begins after the migration of the primordial germ cells (PGCs) into the indifferent gonad. Testis determination is normally initiated in males by the expression of the SRY gene. In the absence of SRY expression, the bipotential gonad develops as an ovary. Ovarian differentiation is dependent on the presence of germ cells. However, germ cells are not necessary for testicular differentiation. The indifferent genital ducts consist of the mesonephric (Wolffian) ducts and the paramesonephric (Müllerian) ducts. In mammalian embryos, the testis secretes several hormones, such AMH, testosterone, and INSL3, which promote Wolffian duct differentiation into the male reproductive tract, whereas the Müllerian ducts degenerate in males. In the absence of the male hormones, the Wolffian ducts degenerate, whereas the Müllerian ducts persist and differentiate into the female internal reproductive tract. The fate of the indifferent genital ducts depends on the gender of the gonad. Genital duct development is a hormonally and genetically controlled process. Hox gene family members are involved in the development of genital ducts in both males and females. Along the anterior–posterior axis of the genital duct, Hox genes are expressed according to their 3’-5’ order in the Hox clusters. Wnt gene family members are also involved in both female gonadal differentiation and female genital duct development. The external genitalia pass through an undifferentiated state before the distinguishing sexual characteristics appear. The development of the genital tubercle is initially regulated by Hox gene expression. Because the genital tubercle is located at the terminal part of the urogenital system, it expresses the 5’-most genes from the Hox gene clusters, specifically Hoxa-13 and Hoxd-13. Malformations of the genital system are intrinsic defects in the developing human that result in localized abnormalities during the development of the reproductive duct system. The genetic abnormalities, such as chromosomal anomalies and gene mutations, influence the development of the genital system and cause malformations.