REPRODUCTIONREVIEW Forkhead transcription factors in ovarian function Nina Henriette Uhlenhaut and Mathias Treier Max Delbru¨ck Center for Molecular Medicine, Robert Ro¨ssle Straße 10, 13125 Berlin-Buch, Germany Correspondence should be addressed to N H Uhlenhaut; Email:
[email protected] Abstract Since the discovery of the conserved forkhead (Fkh) DNA binding domain more than 20 years ago, members of the Fkh or forkhead box (FOX) family of transcription factors have been shown to act as important regulators of numerous developmental and homeostatic processes. The human genome contains 44 Fkh genes, several of which have recently been reported to be essential for female fertility. In this review, we highlight the roles of specific FOX proteins in ovarian folliculogenesis and present our current understanding of their molecular function. In particular, we describe what we have learned from loss-of-function studies using mouse models as well as human genetics and illustrate how different stages of folliculogenesis, both in oocytes and in somatic granulosa and theca cells, are regulated by FOXC1, FOXL2, and FOXO subfamily members. Reproduction (2011) 142 489–495 Introduction stages of folliculogenesis. This transition is marked by oocyte growth and proliferation of the adjacent granu- Female fertility depends on a delicate balance of losa cells that become cuboidal. Antral follicles are hormonal stimuli and cellular interactions, which formed when fluid-filled spaces develop between the ultimately enable conception and a successful preg- multi-layered granulosa cells. During preantral to antral nancy. Current estimates state that 10–15% of couples transition, the oocyte resumes meiosis, and after worldwide remain childless due to infertility, with stimulation by pituitary gonadotropins, FSH, and LH, genetic etiology making up a significant proportion the mature oocyte is expelled from the follicle and moves (Matzuk & Lamb 2002).