Autophagy is essential for preimplantation development of mouse embryos

Science. 2008 Jul 4;321(5885):117-20. doi: 10.1126/science.1154822.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy*
  • Autophagy-Related Protein 5
  • Blastocyst / physiology*
  • Cells, Cultured
  • Embryonic Development*
  • Female
  • Fertilization
  • Lysosomes / physiology
  • Lysosomes / ultrastructure
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Oocytes / physiology
  • Parthenogenesis
  • Phagosomes / physiology
  • Phagosomes / ultrastructure
  • Pregnancy
  • Protein Biosynthesis
  • Proteins / metabolism
  • Recombinant Fusion Proteins / metabolism

Substances

  • Atg5 protein, mouse
  • Autophagy-Related Protein 5
  • Map1lc3b protein, mouse
  • Microtubule-Associated Proteins
  • Proteins
  • Recombinant Fusion Proteins