The pathway to femaleness: current knowledge on embryonic development of the ovary

Abstract

Increasing evidence indicates that organogenesis of the ovary is not a passive process arising by default in the absence of the testis pathway. A coordinated interaction is actually in force between somatic cells and female germ cells in embryonic ovaries, thus creating a unique microenvironment that facilitates the formation of follicles. Identification of the functional roles of several novel regulatory elements such as Figalpha, Foxl2, follistatin, and Wnt4 reveals the complexity of early ovarian organization. Challenges await us to establish the molecular connections of these molecules as well as to discover new candidates in the pathway of early ovarian development.

Fig. 1

A time course of events during embryonic development of the mouse ovary from embryonic day 11 (E11) to birth. Female germ cells (in pink) enter meiosis I around E13.5 and arrest at the dictyate at birth. At ~E15, Figα, a transcription factor specific for female germ cells, begins to be expressed and is essential for production of the zona pellucida (ZP) proteins and formation of primordial follicles at birth. In the somatic cell lineage (in green), WNT4 is produced which is postulated as an autocrine factor to induce the subsequent production of follistatin (FST) starting at E11.5. WNT4 and FST antagonize the formation of testis vasculature and at the same time, maintain the survival of female germ cells at ~E16. FOXL2, a transcription factor specific for female somatic cells, start to appear at ~E12. FOXL2 is critical for further differentiation of pregranulosa cells. Horizontal bars represent the expression of specific genes and occurrence of molecular events.