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Science 4 July 2008:
Vol. 321. no. 5885, pp. 117 - 120
DOI: 10.1126/science.1154822

Reports

Autophagy Is Essential for Preimplantation Development of Mouse Embryos

Satoshi Tsukamoto,1* Akiko Kuma,1,2{dagger} Mirei Murakami,1 Chieko Kishi,1 Akitsugu Yamamoto,3 Noboru Mizushima1,2{ddagger}

After fertilization, maternal proteins in oocytes are degraded and new proteins encoded by the zygotic genome are synthesized. We found that autophagy, a process for the degradation of cytoplasmic constituents in the lysosome, plays a critical role during this period. Autophagy was triggered by fertilization and up-regulated in early mouse embryos. Autophagy-defective oocytes derived from oocyte-specific Atg5 (autophagy-related 5) knockout mice failed to develop beyond the four- and eight-cell stages if they were fertilized by Atg5-null sperm, but could develop if they were fertilized by wild-type sperm. Protein synthesis rates were reduced in the autophagy-null embryos. Thus, autophagic degradation within early embryos is essential for preimplantation development in mammals.

1 Department of Physiology and Cell Biology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
2 SORST, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan.
3 Department of BioScience, Nagahama Institute of Bio-Science and Technology, Nagahama 526-0829, Japan.

* Present address: Laboratory Animal Sciences Section, National Institute of Radiological Sciences, Chiba 263-8555, Japan.

{dagger} Present address: Genome Research Institute, University of Cincinnati, Cincinnati, OH 45237, USA.

{ddagger} To whom correspondence should be addressed. E-mail: nmizu.phy2{at}tmd.ac.jp

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Science. ISSN 0036-8075 (print), 1095-9203 (online)