Autophagy Is Essential for Preimplantation Development of Mouse Embryos

Author:

Tsukamoto Satoshi123,Kuma Akiko123,Murakami Mirei123,Kishi Chieko123,Yamamoto Akitsugu123,Mizushima Noboru123

Affiliation:

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.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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