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

Graduate School of Science and Technology, Kobe University, Kobe 657-8501, Japan and ¹ Graduate School of Biostudies, Kyoto University, Kyoto 606-8507, Japan

Correspondence should be addressed to M Moniruzzaman; Email: 026d910n{at}stu.kobe-u.ac.jp

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 (W^v/W^v:Fas^+/+), Fas-deficient (+/+:Fas^–/–), and both KIT- and Fas-deficient (W^v/W^v: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 W^v/W^v:Fas^–/– genotypes than in W^v/W^v:Fas^+/+ mice at 13 dpc. Furthermore, W^v/W^v: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 W^v/W^v: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.