title: Mechanisms Involved in Porcine Early Embryo Survival following Ethanol Exposure.
abstract: Alcohol consumption during pregnancy is still a cause of preventable birth defects and developmental disabilities. However, little is known about the impact of ethanol on preimplantation embryos and the molecular mechanisms involved. We aimed to determine the toxicogenomic impacts and the mechanisms involved in preimplantation embryonic survival following 0.2% ethanol exposure in porcine embryos. Gene expression changes were measured with a porcine embryo specific microarray and confirmed by RT-qPCR. When compared with control, ethanol exposure led to a 43% decrease in blastocyst rate and activated pathways associated with oxidative stress and nervous system damage, such as TP53 and TGF. Moreover, we observed a mitochondrial dysfunction in the exposed embryos as revealed by the decrease in Mitotracker Red fluorescence intensity (25 and 41% in 4-cell embryos and blastocysts, respectively) and a modification in the expression of GABRB3, APP, CLU, and MIOX genes. We therefore present evidence of neuronal-like adverse effects on undifferentiated cells suggesting that fetal alcohol spectrum disorder could have its origin as early as in the first week postfertilization.
authors.affiliation: Centre de Recherche en Reproduction, Développement et Santé Intergénérationnelle, Université Laval, Québec, Québec G1V 0A6, Canada.
authors.forename: Florence
authors.initials: F
authors.lastname: Pagé-Larivière
authors.affiliation: Institut National de Santé Publique du Québec, Québec and Département de Médecine Sociale et Préventive, Université Laval, Québec, Québec G1V 5B3, Canada.
authors.forename: Céline
authors.initials: C
authors.lastname: Campagna
authors.affiliation: Centre de Recherche en Reproduction, Développement et Santé Intergénérationnelle, Université Laval, Québec, Québec G1V 0A6, Canada.
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Sirard
mesh_terms: D000003:Abattoirs; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051152:Clusterin / Q000235:genetics / Q000378:metabolism; D004477:Ectogenesis / Q000187:drug effects*; D020964:Embryo Loss / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005307:Fertilization in Vitro; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D050562:Inositol Oxygenase / Q000235:genetics / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009028:Morula / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D012997:Solvents / Q000009:adverse effects / Q000633:toxicity*; D034421:Sus scrofa
chemical_list: D016564:Amyloid beta-Protein Precursor; D051152:Clusterin; D011963:Receptors, GABA-A; D012997:Solvents; D000431:Ethanol; D050562:Inositol Oxygenase
keywords: Toxicogenomics; embryo; microarray; neurotoxicity.; predictive toxicology