title: Autophagy regulates embryonic survival during delayed implantation.
abstract: Delayed implantation, considered a state of suspended animation, is widespread in mammals. Blastocysts under this condition remain dormant for an extended period but resume implantation competence upon favorable conditions. The underlying mechanism by which extended longevity of dormant blastocysts is maintained is not clearly understood. Using autophagy markers and the well-defined delayed implantation model in mice, we show that autophagy is important for the extended longevity of dormant blastocysts in utero during delayed implantation. However, prolonged dormancy leads to reduced developmental competency of blastocysts and cellular damage with compromised pregnancy outcome. Estrogen supplementation, which activates implantation of dormant blastocysts, induces the formation of multivesicular bodies in the trophectoderm in vivo. Collectively, our results suggest that autophagy is a critical cellular mechanism that is utilized for the prolonged survival of dormant blastocysts.
authors.affiliation: Department of Biomedical Sciences and Technology, Institute of Biomedical Science and Technology, Research Center for Transcription Control, Kwangjin-gu, Seoul 143-701, Korea. hlim@konkuk.ac.kr
authors.forename: Jong-Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Hyun-Ah
authors.initials: HA
authors.lastname: Oh
authors.forename: Haengseok
authors.initials: H
authors.lastname: Song
authors.forename: Jin Hyun
authors.initials: JH
authors.lastname: Jun
authors.forename: Cheong-Rae
authors.initials: CR
authors.lastname: Roh
authors.forename: Huirong
authors.initials: H
authors.lastname: Xie
authors.forename: S K
authors.initials: SK
authors.lastname: Dey
authors.forename: Hyunjung Jade
authors.initials: HJ
authors.lastname: Lim
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D001755:Blastocyst / Q000378:metabolism* / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D010064:Embryo Implantation / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D057146:Multivesicular Bodies / Q000378:metabolism / Q000648:ultrastructure; D011247:Pregnancy; D013997:Time Factors
chemical_list: D004967:Estrogens; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D049452:Green Fluorescent Proteins; C025946:3-methyladenine; D000225:Adenine