Regulation of follicle growth and apoptosis in cultured mouse ovaries by NGF and oxygen

Abstract

Cryopreservation of ovarian tissue has been proposed for use in preserving female fertility before anticancer chemo-radiotherapy, because ovarian tissue contains a large pool of non-growing, primordial follicles. The mechanisms that regulate the exit of follicles from the pool are poorly understood. To determine optimal conditions for in vitro ovarian culture, we investigated the effects of nerve growth factor (NGF) and oxygen concentration on follicle growth and apoptosis. Oxygen concentration affected both cell proliferation and apoptosis. Under 20% oxygen, but not 1.5% or 5%, NGF decreased apoptosis in mouse ovaries by down-regulating the pro-apoptotic genes Bax and p53. In conclusion, high oxygen tension during in vitro ovarian culture promotes follicle growth and, in conjunction with NGF, suppresses apoptosis. The efficiency of this method to preserve fertility depends in part on the level of atresia. These results suggest that oxygen and NGF may be used to increase numbers of preantral follicles and mature oocytes in the culture of mammalian ovarian cortical strips.