Switch from BAX-dependent to BAX-independent germ cell loss during the development of fetal mouse ovaries

Abstract

Female reproductive life is limited by the oocyte/follicle pool, which has been determined by the number of germ cells to enter meiosis and subsequent loss of oocytes. It has been suggested that apoptosis accounts for the elimination of germ cells throughout oogenesis. However, female germ cells are lost continuously while they undergo distinct cell cycles in fetal and neonatal life. No convincing evidence has yet been provided to show apoptotic death of oocytes during meiotic prophase in vivo. In this study, we examined the change in the germ cell population in mice deficient of BAX, a key proapoptotic molecule. The number of germ cells, identified by GCNA1 immunolabeling, approximately doubled in ovaries of Bax-/- mice compared with ovaries of heterozygous Bax+/- mice and wild-type Bax+/+ mice by 14.5 days post coitum (d.p.c.) and remained higher up to 24.5 d.p.c. However, there was a rapid loss of germ cells in Bax-/- ovaries, paralleling that in Bax+/-and Bax+/+ ovaries from 14.5-24.5 d.p.c., a period in which most germ cells entered and progressed in meiotic prophase. These results suggest that, while progressing through meiotic prophase, oocytes are eliminated by a BAX-independent mechanism.