WNT4 Signaling in Female Gonadal Development

Miriam      Pellegrino; Raffaella      Maiorino; Sergio      Schonauer

Abstract

WNT4 signaling pathways represent an important step in the multi-faceted process of mammalian gonadal differentiation and the development of internal genitalia. WNT4 protein controls the cytoplasmatic stability of specific transcriptional coactivator β catenin during both embriogenesis and adult homeostasis. The biological significance of WNT4 consists in determining the final female reproductive system, inhibiting Wolff ducts differentiation, male steroidogenesis and vascular cell migration. An overview of WNT4 cellular mechanisms is given in order to understand its critical role in the genesis of various human diseases such as congenital malformations and gynecological disorders like polycystic ovary syndrome (PCOS). The final discussion focusses on several possible therapeutic uses of Wnt4 both during pregnancy in order to correct the genetic loss of function of the protein and during adulthood in order to normalize fertility in PCOS-affected females planning pregnancy.

Keywords: Wnt4, β catenin, frizzled, pathway, female development, Mayer — Rokitansky — Kuster — Hauser syndrome, SERKAL syndrome, polycystic ovary disease