Oocyte growth and follicular development in KIT-deficient Fas-knockout mice

Abstract

In mammals, oocyte growth and follicular development are known to be regulated by KIT, a tyrosine kinase receptor. Fas is a member of the death receptor family inducing apoptosis. Here, we investigated germ cell survival, oocyte growth and follicular development in KIT-deficient (Wv/Wv:Fas+/+), Fas-deficient (+/+:Fas-/-), and both KIT- and Fas-deficient (Wv/Wv:Fas-/-) mice during fetal and postnatal periods. Further, the ovaries of these mice were transplanted in immunodeficient mice to compare oocyte growth and follicular development under a condition isolated from the extraovarian effects of KIT- and Fas-deficiency. Higher numbers of germ cells were found in the fetal and postnatal ovaries of Fas-deficient mice than in the same-aged wild-type mice. In KIT-deficient mice, ovaries at 13 days postcoitum (dpc) contained 1106 ± 72 (n= 3) germ cells, but the ovaries contained no oocytes after birth. Twenty-one days after transplantation of the ovaries at 13 dpc, no oocytes/germ cells were found. A higher number of germ cells (3843 ± 108; n = 3) were observed in the Wv/Wv:Fas-/- genotypes than in Wv/Wv:Fas+/+ mice at 13 dpc. Furthermore, Wv/ Wv:Fas-/- mice contained 528 ± 91 (n = 3) oocytes at 2 days, and follicles developed to the antral stage at 14 days of age. After transplantation of fetal and neonatal ovaries from Wv/Wv:Fas-/- mice, increased numbers of growing oocytes and developing follicles were obtained compared with those in 14-day old ovaries in vivo. These results show that oocytes grow and follicles develop without KIT signaling, although KIT might be essential for the survival of germ cells/oocytes in mice. © 2007 Society for Reproduction and Fertility.