title: Uncovering a role for endocannabinoid signaling in autophagy in preimplantation mouse embryos.
abstract: Endocannabinoid signaling plays various roles in directing reproductive processes. Mouse embryos are shown to express high levels of CB1 receptor (CB1R). Low concentrations of anandamide stimulate embryo growth and implantation but at higher concentrations it adversely affects implantation. We tested the hypothesis that high levels of endocannabinoids cause autophagic activation and cell death in preimplantation mouse embryos. We used methanandamide (METH), a selective CB1R agonist, to examine the effect of heightened endocannabinoid signaling on autophagy in mouse embryos. Western blotting, immunofluorescence staining, transmission electron microscopy and TUNEL analysis were performed. We observed that METH treatment in vitro or in vivo up-regulated autophagic response in preimplantation mouse embryos. In blastocysts, apoptosis was also increased after METH injections. At 28 nM, which is considered a high physiological dose to embryonic cells, METH up-regulated autophagic activation in trophoblast stem cells. This work demonstrates for the first time that blastocysts respond to higher than normal levels of endocannabinoid by increasing autophagic activation and apoptosis.
authors.affiliation: Department of Biomedical Science & Technology, SMART Institute of Advanced Biomedical Science,  Konkuk University, 120 Neungdong-ro, Kwangjin-gu, Seoul 143-701,  Korea.
authors.forename: Hyun-Ah
authors.initials: HA
authors.lastname: Oh
authors.forename: Sojung
authors.initials: S
authors.lastname: Kwon
authors.forename: Soyoung
authors.initials: S
authors.lastname: Choi
authors.forename: Hyejin
authors.initials: H
authors.lastname: Shin
authors.forename: Kwang Ho
authors.initials: KH
authors.lastname: Yoon
authors.forename: Wan Jong
authors.initials: WJ
authors.lastname: Kim
authors.forename: Hyunjung Jade
authors.initials: HJ
authors.lastname: Lim
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001755:Blastocyst / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D063388:Endocannabinoids / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005455:Fluorescent Antibody Technique; D051379:Mice; D008813:Mice, Inbred ICR; D046529:Microscopy, Electron, Transmission; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; C078814:anandamide