title: Retinoic acid influences the embryoid body formation in mouse embryonic stem cells by induction of caspase and p38 MAPK/JNK-mediated apoptosis.
abstract: Although all-trans retinoic acid (RA), the oxidative metabolite of vitamin A, is essential for normal development, high levels are teratogenic in many species. RA results in immediate effects on the preimplantation embryo and on blastocyst development in vitro and in vivo. To further elucidate the cellular mechanisms of early postimplantation embryo development induced by RA, we present an embryonic cell line, B5, as a candidate system for the investigation of these processes. We used undifferentiated ES cells as the model, which is from the undifferentiated status to differentiated status [embryoid body (EB) formation] mimicking postimplantation embryo development (egg-cylinder stage of embryo formation) to clarify the cellular mechanism of action of RA in the implanted blastocysts and cell apoptosis following the series of exposures to differing RA concentrations. Using an in vitro model, we identified the impact of RA on undifferentiated embryonic stem (ES) cells, including inhibition of cell proliferation and induction of cell apoptosis. JNK, P-38 and caspase activation were shown in the nature of RA-triggered apoptotic signaling in ES cells. The carry-on influences of RA on the ES cell were shown in the formation of EB from the pretreated ES cells. RA resulted in apparent impact on undifferentiated ES cells in vitro, with increased numbers of apoptotic cells initially and inhibited cell proliferation, which led to decreased size of EB. The process of EB formation (mimicking the early postimplantation embryo development) is regulated by RA-induced apoptosis through the activation of caspase and P38 MAPK/JNK pathway.
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Taiwan. huangfj@seed.net.tw
authors.forename: Fu-Jen
authors.initials: FJ
authors.lastname: Huang
authors.forename: Kuo-Chung
authors.initials: KC
authors.lastname: Lan
authors.forename: Hong-Yo
authors.initials: HY
authors.lastname: Kang
authors.forename: Pin-Yao
authors.initials: PY
authors.lastname: Lin
authors.forename: Wen-Hsiung
authors.initials: WH
authors.lastname: Chan
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Hsu
authors.forename: Yen-Chih
authors.initials: YC
authors.lastname: Liu
authors.forename: Ko-En
authors.initials: KE
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D058732:Embryoid Bodies / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004790:Enzyme Induction; D005260:Female; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D011247:Pregnancy; D014212:Tretinoin / Q000633:toxicity*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
chemical_list: D014212:Tretinoin; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases