title: Ethanol cytotoxic effect on trophoblast cells.
abstract: Prenatal ethanol exposure may cause both, altered fetal neurodevelopment and impaired placental function. These disturbances can lead to growth retardation, which is one of the most prevalent features in Fetal Alcohol Syndrome (FAS). It is not known whether there is a specific pattern of cytotoxicity caused by ethanol that can be extrapolated to other cell types. The aim of this study was to determine the cytotoxic effects caused by sustained exposure of trophoblast cells to ethanol. The cytotoxic effect of sustained exposure to standard doses of ethanol on an in vitro human trophoblast cell line, JEG3, was examined. Viable cell count by exclusion method, total protein concentration, lactate dehydrogenase (LDH) activity and activation of apoptotic markers (P-H2AX, caspase-3 and PARP-1) were determined. Sustained exposure to ethanol decreased viable cell count and total protein concentration. LDH activity did not increased in exposed cells but apoptotic markers were detected. In addition, there was a dose-dependent relationship between ethanol concentration and apoptotic pathways activation. Sustained ethanol exposure causes cellular cytotoxicity by apoptotic pathways induction as a result of DNA damage. This apoptotic induction may partially explain the altered function of placental cells and the damage previously detected in other tissues.
authors.affiliation: Unitat de Recerca Infància i Entorn (URIE), Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), PRBB, C/ Dr. Aiguader 88, 08003 Barcelona, Spain; Red de Salud Materno Infantil y del Desarrollo (SAMID), Programa RETIC, Instituto Carlos III, C/ Sinesio Delgado 4, 28029 Madrid, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Clave
authors.affiliation: Unitat de Recerca Infància i Entorn (URIE), Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), PRBB, C/ Dr. Aiguader 88, 08003 Barcelona, Spain; Red de Salud Materno Infantil y del Desarrollo (SAMID), Programa RETIC, Instituto Carlos III, C/ Sinesio Delgado 4, 28029 Madrid, Spain.
authors.forename: X
authors.initials: X
authors.lastname: Joya
authors.affiliation: Unitat de Recerca Infància i Entorn (URIE), Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), PRBB, C/ Dr. Aiguader 88, 08003 Barcelona, Spain; Red de Salud Materno Infantil y del Desarrollo (SAMID), Programa RETIC, Instituto Carlos III, C/ Sinesio Delgado 4, 28029 Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Salat-Batlle
authors.affiliation: Unitat de Recerca Infància i Entorn (URIE), Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), PRBB, C/ Dr. Aiguader 88, 08003 Barcelona, Spain; Red de Salud Materno Infantil y del Desarrollo (SAMID), Programa RETIC, Instituto Carlos III, C/ Sinesio Delgado 4, 28029 Madrid, Spain; Departament de Pediatria, Obstetricia i Ginecologia, i Medicina Preventiva, Universitat Autònoma de Barcelona (UAB), Campus M, 08193 Bellaterra, Spain. Electronic address: 90458@hospitaldelmar.cat.
authors.forename: O
authors.initials: O
authors.lastname: Garcia-Algar
authors.affiliation: Unitat de Recerca Infància i Entorn (URIE), Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), PRBB, C/ Dr. Aiguader 88, 08003 Barcelona, Spain; Red de Salud Materno Infantil y del Desarrollo (SAMID), Programa RETIC, Instituto Carlos III, C/ Sinesio Delgado 4, 28029 Madrid, Spain; Departament de Pediatria, Obstetricia i Ginecologia, i Medicina Preventiva, Universitat Autònoma de Barcelona (UAB), Campus M, 08193 Bellaterra, Spain.
authors.forename: O
authors.initials: O
authors.lastname: Vall
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000209:etiology / Q000473:pathology; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: C468783:H2AX protein, human; D006657:Histones; D000431:Ethanol; D007770:L-Lactate Dehydrogenase; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: Alcohol; Apoptosis; Cytotoxic effect; Ethanol; Placenta; Trophoblast