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.
Tsukamoto
Satoshi
S
Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo, Japan.
Kuma
Akiko
A
Mizushima
Noboru
N
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