The role of autophagy during the oocyte-to-embryo transition.
After fertilization, the maternal proteins stored in oocytes are degraded and new proteins encoded by the zygotic genome are synthesized. Although several proteins are degraded by the ubiquitin-proteasome system, the mechanism underlying the dynamic protein turnover during this process remains largely unknown. We recently reported that autophagy plays a critical role during preimplantation embryonic development. We found that the level of autophagy was low in unfertilized oocytes; however, autophagy was activated shortly after fertilization. The function of autophagy was further analyzed using oocyte-specific Atg5 (autophagy-related 5) knockout mice. Atg5-null oocytes could develop if they were fertilized with wild-type sperm, but could not develop beyond the four- and eight-cell stages if they were fertilized with Atg5-null sperm. Furthermore, protein synthesis rates were 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(-/-) neonates, emphasizing the specific importance of autophagy during very early embryogenesis. Thus, the degradation of maternal factors by autophagy is essential for preimplantation development in mammals.
Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo, Japan.
Satoshi
S
Tsukamoto
Akiko
A
Kuma
Noboru
N
Mizushima
D000818:Animals; D001343:Autophagy / Q000235:genetics; D000071187:Autophagy-Related Protein 5; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D047108:Embryonic Development / Q000235:genetics; D005306:Fertilization; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009865:Oocytes / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D011506:Proteins / Q000378:metabolism*
C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; D011506:Proteins