title: Induction of autophagy promotes preattachment development of bovine embryos by reducing endoplasmic reticulum stress.
abstract: The coupling of autophagy and endoplasmic reticulum (ER) stress has been implicated in a variety of biological processes; however, little is known regarding the involvement of the autophagy/ER stress pathway in early embryogenesis or the underlying mechanism(s). Here, we showed that the developmental competence of in vitro-produced (IVP) bovine embryos was highly dependent on the autophagy/ER stress balance. Although relative abundances of autophagy-associated gene transcripts, including LC3, Atg5, and Atg7 transcripts, were high in oocytes and throughout the early stages of preattachment development, extensive autophagosome formation was only detected in fertilized embryos. Using an inducer and inhibitor of autophagy, we showed that transient elevation of autophagic activity during early preattachment development greatly increased the blastocyst development rate, trophectoderm cell numbers, and blastomere survival; these same parameters were reduced by both inhibition and prolonged induction of autophagy. Interestingly, the induction of autophagy reduced ER stress and associated damage, while the developmental defects in autophagy-inhibited embryos were significantly alleviated by ER stress inhibitor treatment, indicating that autophagy is a negative regulator of ER stress in early embryos. Collectively, these results suggest that early embryogenesis of IVP bovine embryos depends on an appropriate balance between autophagy and ER stress. These findings may increase our understanding of important early developmental events by providing compelling evidence concerning the tight association between autophagy and ER stress, and may contribute to the development of strategies for the production of IVP bovine blastocysts with high developmental competence.
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do, Republic of Korea.
authors.forename: Bong-Seok
authors.initials: BS
authors.lastname: Song
authors.forename: Seung-Bin
authors.initials: SB
authors.lastname: Yoon
authors.forename: Ji-Su
authors.initials: JS
authors.lastname: Kim
authors.forename: Bo-Woong
authors.initials: BW
authors.lastname: Sim
authors.forename: Young-Hyun
authors.initials: YH
authors.lastname: Kim
authors.forename: Jae-Jin
authors.initials: JJ
authors.lastname: Cha
authors.forename: Seon-A
authors.initials: SA
authors.lastname: Choi
authors.forename: Hyun-Ki
authors.initials: HK
authors.lastname: Min
authors.forename: Youngjeon
authors.initials: Y
authors.lastname: Lee
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Huh
authors.forename: Sang-Rae
authors.initials: SR
authors.lastname: Lee
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Deog-Bon
authors.initials: DB
authors.lastname: Koo
authors.forename: Young-Kug
authors.initials: YK
authors.lastname: Choo
authors.forename: Hwan Mook
authors.initials: HM
authors.lastname: Kim
authors.forename: Sun-Uk
authors.initials: SU
authors.lastname: Kim
authors.forename: Kyu-Tae
authors.initials: KT
authors.lastname: Chang
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D001757:Blastomeres / Q000166:cytology / Q000378:metabolism; D002417:Cattle; D002452:Cell Count; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology*; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D005260:Female; D005307:Fertilization in Vitro; D018507:Gene Expression Regulation, Developmental; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008954:Models, Biological; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics
chemical_list: D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D044764:Ubiquitin-Activating Enzymes