Funntion of autophagy during oocyte-to-embryo transition in mice

Oocytes accumulate maternal proteins necessary for oogenesis. After fertilization, however, the stores of maternal proteins are rapidly degraded and new proteins encoded by the zygotic genome are translated. Although several proteins have been demonstrated to be degraded by the ubiquitin-proteasome pathway, the mechanism underlying the dynamic protein turnover during this process remains largely unknown. We will report in this meeting that autophagy plays a critical role during the oocyte-to-embryo transition period. Autophagy is the major route for the degradation of cytoplasmic constituents in the lysosome, which is known to be important for various cellular functions such as starvation adaptation, intracellular protein quality control1. We found that the level of autophagy was low in unfertilized oocytes, however, autophagy is activated shortly after fertilization2. The importance of the autophagy during the early embryogenesis was further analyzed using oocyte-specific Atg5 (autophagy related 5) knockout mice. Oocytes lacking Atg5 could develop if they were fertilized with wild-type sperm, but could not develop beyond the four- to eight-cell stages if they were fertilized with Atg5-null sperm. Furthermore, proteins synthesis rate reduced in the autophagy-deficient embryos. We have previously reported that Atg5-null oocytes derived from Atg5+/- mice, which should contain maternally inherited Atg5 protein in the oocyte, were able to produce Atg5-/- neonates3, emphasizing the specific importance of autophagy during the very early embryogenesis. Thus, the degradation of maternal factors by autophagy is essential for preimplantation development in mammals.The fifth annual conference of the asian reproductive biotechnology society（第五回アジア繁殖技術学会