Induction of autophagy improves embryo viability in cloned mouse embryos

• Published in: Scientific reports Vol. 5; no. 1; p. 17829
• Main Authors: Shen, XingHui, Zhang, Na, Wang, ZhenDong, Bai, GuangYu, Zheng, Zhong, Gu, YanLi, Wu, YanShuang, Liu, Hui, Zhou, DongJie, Lei, Lei
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.12.2015; Nature Publishing Group
• Subjects: 13/1; 38/77; 631/136/1455; 631/136/2435; 64/60; 82/51; 82/80; Actin; Actin Cytoskeleton - metabolism; Animals; Autophagy; Autophagy - drug effects; Autophagy - genetics; Cloning, Organism; Cytochalasin B; Demethylation; Deoxyribonucleic acid; Depolymerization; DNA; DNA Methylation; Embryo, Mammalian; Embryos; Female; Fertilization in Vitro; Filaments; Gene Expression; Humanities and Social Sciences; Male; Mechanistic Target of Rapamycin Complex 1; Mice; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; mRNA; multidisciplinary; Multiprotein Complexes - antagonists & inhibitors; Nuclear transfer; Nuclear Transfer Techniques; Oocytes; Oocytes - metabolism; Organelles; Phagocytosis; Protein Kinase Inhibitors - pharmacology; Rapamycin; RNA Stability - drug effects; RNA, Messenger - genetics; RNA, Messenger - metabolism; Science; Sirolimus - pharmacology; Somatic cell nuclear transfer; TOR Serine-Threonine Kinases - antagonists & inhibitors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep17829

Autophagy is an essential cellular mechanism that degrades cytoplasmic proteins and organelles to recycle their components. Moreover, autophagy is essential for preimplantation development in mammals. Here we show that autophagy is also important for reprogramming in somatic cell nuclear transfer (SCNT). Our data indicate that unlike fertilized oocytes, autophagy is not triggered in SCNT embryos during 6 hours of activation. Mechanistically, the inhibited autophagic induction during SCNT activation is due to the cytochalasin B (CB) caused depolymerization of actin filaments. In this study, we induced autophagy during SCNT activation by rapamycin and pp242, which could restore the expected level of autophagy and significantly enhance the development of SCNT embryos to the blastocyst stage when compared with the control (68.5% and 68.7% vs. 41.5%, P  < 0.05). Furthermore, the treatment of rapamycin and pp242 accelerates active DNA demethylation indicated by the conversion of 5 mC to 5 hmC and treatment of rapamycin improves degradation of maternal mRNA as well. Thus, our findings reveal that autophagy is important for development of SCNT embryos and inhibited autophagic induction during SCNT activation might be one of the serious causes of low efficiency of SCNT.