怀孕前后酒精摄入对雌鼠植入前胚胎DNA甲基化模式建立的影响

Female Rats Ingested Alcohol before and after Pregnancy Impact DNA Methylation Patterns in Pre-implantation Embryo

女性怀孕前后饮酒会对胎儿的发育及神经系统造成不利影响,称为"胎儿酒精综合征"(fetal alcohol spectrum disorders,FASD)。小鼠通常作为研究该病的动物模型。该实验采用体外培养技术及体内冲胚法研究雌鼠怀孕前后酒精摄入对各期植入前胚胎全基因组DNA甲基化模式建立的影响。小鼠植入前胚胎体外培养实验发现,体外实验组I(怀孕前酒精处理组),除8-cell外,其他各期胚胎的DNA甲基化水平明显低于体外对照组;体外实验组II(正常胚胎在含乙醇的培养基中培养),各期植入前胚胎DNA甲基化水平均明显低于体外对照组。体内实验发现,体内实验组I(怀孕前酒精处理组)与体内的实验组II(怀孕后酒精处理组),各期植入前胚胎DNA甲基化水平明显低于体内对照组。体内、外实验结果表明:受精前后酒精对各期植入前胚胎DNA甲基化模式的正确建立造成紊乱,该结果可为进一步揭示FSAD发病机制提供一定的实验基础。

Women exposed to alcohol before and after pregnancy have been found to impede the fetal development and adversely affect its nervous system, known as fetal alcohol syndrome disorders. Mice often used as an animal model of the disease. As part of our investigation of mechanisms underlying alcohol adverse effects on DNA methylation patterns in pre-implantation embryos, embryos in vitro and in vivo from female mice intaked alcohol before and after pregnancy were studied. We found that treatment group I in vitro （long-term alcohol intake before pregnancy）, except for 8-cell, the embryonic DNA methylation levels were significantly lower than the con- trol group; Treatment group II in vitro （embryos cultured in a medium contained ethanol） was significantly lower than the control group in every period of time. Compare treatment group I and treatment group II in vivo found that DNA methylation in pre-implantation embryo was significantly lower than the control in vivo. Experimental results in vivo and in vitro indicated that females before and after pregnancy with alcohol intake might cause incorrect establishment of DNA methylation patterns in pre-implantation embryo, which provided certain foundation for revealing certain basic mechanisms of fetal alcohol syndrome.