Pagé-Larivière Florence, Campagna Céline, Sirard Marc-André
Centre de Recherche en Reproduction, Développement et Santé Intergénérationnelle, Université Laval, Québec, Québec G1V 0A6, Canada.
Institut National de Santé Publique du Québec, Québec and Département de Médecine Sociale et Préventive, Université Laval, Québec, Québec G1V 5B3, Canada.
Toxicol Sci. 2017 Mar 1;156(1):289-299. doi: 10.1093/toxsci/kfw256.
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.
孕期饮酒仍是可预防的出生缺陷和发育障碍的一个原因。然而，关于乙醇对植入前胚胎的影响以及所涉及的分子机制，人们了解甚少。我们旨在确定在猪胚胎中暴露于0.2%乙醇后对植入前胚胎存活的毒理基因组影响及相关机制。用猪胚胎特异性微阵列测量基因表达变化，并通过RT-qPCR进行确认。与对照组相比，乙醇暴露导致囊胚率降低43%，并激活了与氧化应激和神经系统损伤相关的通路，如TP53和TGF。此外，我们观察到暴露胚胎中的线粒体功能障碍，这表现为Mitotracker Red荧光强度降低（4细胞胚胎和囊胚中分别降低25%和41%）以及GABRB3、APP、CLU和MIOX基因表达的改变。因此，我们提供了对未分化细胞有类似神经元不良影响的证据，表明胎儿酒精谱系障碍可能早在受精后第一周就已产生。
