Creation of rescue system for potential oocytes by apoptosis inhibitory factor gene transfer and xenotransplantation techniques

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In mammals, hundreds of thousands of oocytes are contained in adult ovaries, and small part of oocytes restart meiosis in each estrous cycle. More than 99% of follicles are regenerated as atresia, however, molecular control mechanism to select ovulating oocytes which is an important strategy to get excellent offspring has not been revealed. The present study performed to elucidate the molecular control mechanism that regulates a selective killing of ovarian follicles in porcine ovaries, in other words, to examine the apoptosis regulating molecular mechanism in granulosa cells. I analyzed the transmission system of apoptotic signal in granulosa cells. I revealed that granulosa cell was a type II apoptosis cell in which apoptotic signal transduced via mitochondria. I found that a novel soluble receptor, an outside factor of cell membrane, inhibited cell death in garnulosa cells. Moreover, I demonstrated two inhibitors, cFLIP and XIAP, which interrupted apoptotic signaling within the cells. For application of these apoptosis inhibiting factors, I created the rescue system for potential oocytes in frozen small ovarian tissues by apoptosis inhibitory factor gene transfer and xenotransplantation techniques to raise the follicle survival rate.