Autophagy Is Essential for Preimplantation Development of Mouse Embryos

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]  Z. Elazar,et al.  Utilizing flow cytometry to monitor autophagy in living mammalian cells , 2008, Autophagy.

[2]  Daniel J. Klionsky,et al.  Autophagy fights disease through cellular self-digestion , 2008, Nature.

[3]  N. Mizushima,et al.  Autophagy: process and function. , 2007, Genes & development.

[4]  Daniel J. Klionsky,et al.  Autophagy: from phenomenology to molecular understanding in less than a decade , 2007, Nature Reviews Molecular Cell Biology.

[5]  Geraldine Seydoux,et al.  Regulation of the Oocyte-to-Zygote Transition , 2007, Science.

[6]  Alexander F Schier,et al.  The Maternal-Zygotic Transition: Death and Birth of RNAs , 2007, Science.

[7]  M. Matsui,et al.  LC3, an Autophagosome Marker, Can be Incorporated into Protein Aggregates Independent of Autophagy: Caution in the Interpretation of LC3 Localization , 2007, Autophagy.

[8]  Hideyuki Okano,et al.  Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice , 2006, Nature.

[9]  N. Mizushima,et al.  Generation of cell lines with tetracycline‐regulated autophagy and a role for autophagy in controlling cell size , 2006, FEBS letters.

[10]  T. Ueno,et al.  Lysosomal Turnover, but Not a Cellular Level, of Endogenous LC3 is a Marker for Autophagy , 2005, Autophagy.

[11]  Wael Tadros,et al.  Setting the stage for development: mRNA translation and stability during oocyte maturation and egg activation in Drosophila , 2005, Developmental dynamics : an official publication of the American Association of Anatomists.

[12]  Takeshi Tokuhisa,et al.  The role of autophagy during the early neonatal starvation period , 2004, Nature.

[13]  Geraldine Seydoux,et al.  A clean start: degradation of maternal proteins at the oocyte-to-embryo transition. , 2004, Trends in cell biology.

[14]  Daniel J Klionsky,et al.  Development by self-digestion: molecular mechanisms and biological functions of autophagy. , 2004, Developmental cell.

[15]  A. Cuervo Autophagy: in sickness and in health. , 2004, Trends in cell biology.

[16]  M. Matsui,et al.  In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. , 2003, Molecular biology of the cell.

[17]  A. Prescott,et al.  Inhibition of Autophagy in Mitotic Animal Cells , 2002, Traffic.

[18]  Takeshi Tokuhisa,et al.  Dissection of Autophagosome Formation Using Apg5-Deficient Mouse Embryonic Stem Cells , 2001, The Journal of cell biology.

[19]  A. Yamamoto,et al.  Acidic endomembrane organelles are required for mouse postimplantation development. , 2000, Developmental biology.

[20]  Takeshi Noda,et al.  LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing , 2000, The EMBO journal.

[21]  J. Dean,et al.  Expression of Cre recombinase in mouse oocytes: A means to study maternal effect genes , 2000, Genesis.

[22]  K. Swann,et al.  Calcium oscillations and protein synthesis inhibition synergistically activate mouse oocytes , 1995, Molecular reproduction and development.

[23]  R. Brinster,et al.  Protein degradation during preimplantation development of the mouse. , 1981, Journal of reproduction and fertility.