Kalisch-Smith J I, Moritz K M
a School of Biomedical Sciences, The University of Queensland, St. Lucia, QLD 4072, Australia.
b Child Health Research Centre, The University of Queensland, South Brisbane, QLD 4101, Australia.
Biochem Cell Biol. 2018 Apr;96(2):107-116. doi: 10.1139/bcb-2017-0133. Epub 2017 Nov 7.
In western countries, alcohol consumption is widespread in women of reproductive age, and in binge quantities. These countries also continue to have high incidences of unplanned pregnancies, with women often reported to cease drinking after discovering their pregnancy. This suggests the early embryo may be highly exposed to the detrimental effects of alcohol during the periconception period. The periconception and pre-implantation windows, which include maturation of the oocyte, fertilisation, and morphogenesis of the pre-implantation embryo, are particularly sensitive times of development. Within the oviduct and uterus, the embryo is exposed to a unique nutritional environment to facilitate its development and establish de-novo expression of the genome through epigenetic reprogramming. Alcohol has wide-ranging effects on cellular stress, as well as hormonal, and nutrient signalling pathways, which may affect the development and metabolism of the early embryo. In this review, we summarise the adverse developmental outcomes of early exposure to alcohol (prior to implantation in animal models) and discuss the potential mechanisms for these outcomes that may occur within the protected oviductal and uterine environment. One interesting candidate is reduced retinoic acid synthesis, as it is implicated in the control of epigenetic reprogramming and cell lineage commitment, processes that have adverse consequences for the formation of the placenta, and subsequently, fetal programming.
在西方国家，育龄女性中酒精消费普遍且存在暴饮现象。这些国家意外怀孕的发生率也持续居高，常有报道称女性在发现怀孕后就停止饮酒。这表明早期胚胎在受孕期间可能高度暴露于酒精的有害影响之下。受孕和植入前阶段，包括卵母细胞成熟、受精以及植入前胚胎的形态发生，是发育过程中特别敏感的时期。在输卵管和子宫内，胚胎暴露于独特的营养环境中，以促进其发育并通过表观遗传重编程建立基因组的从头表达。酒精对细胞应激以及激素和营养信号通路有广泛影响，这可能会影响早期胚胎的发育和代谢。在本综述中，我们总结了早期暴露于酒精（在动物模型中植入前）的不良发育后果，并讨论了这些后果可能在受保护的输卵管和子宫环境中发生的潜在机制。一个有趣的候选机制是视黄酸合成减少，因为它与表观遗传重编程和细胞谱系定向控制有关，而这些过程会对胎盘形成以及随后的胎儿编程产生不良后果。
