Detrimental effects of alcohol exposure around conception: putative mechanisms

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. Key words: ethanol, programming, embryo, epigenetics, retinoic acid. Dans les pays occidentaux, la consommation d'alcool en quantite excessive est repandue chez les femmes en age de procreer. Ces pays continuent aussi de presenter une haute incidence de grossesses non planifiees, les femmes rapportant souvent cesser l'alcool apres avoir appris qu'elles etaient enceintes. Cela suggere que l'embryon precoce peut avoir ete hautement expose aux effets nocifs de l'alcool durant la periconception. La fenetre situee entre la periconception et la preimplantation, qui comprend la maturation de l'ovocyte, la fertilisation et la morphogenese de l'embryon avant l'implantation, est une periode particulierement sensible du developpement. A l'interieur de l'oviducte et de l'uterus, l'embryon est expose a un environnement nutritionnel unique qui facilite son developpement et etablit l'expression de novo du genome a travers la reprogrammation epigenetique. L'alcool exerce des effets multiples sur le stress cellulaire et sur les voies de signalisation hormonales et nutritionnelles, qui peuvent affecter le developpement et le metabolisme de cet embryon precoce. Dans cette synthese, les auteurs resument les consequences developpementales indesirables de l'exposition precoce a l'alcool avant l'implantation dans des modeles animaux, et discutent des mecanismes potentiels qui peuvent survenir a l'interieur de l'environnement protege de l'oviducte et de l'uterus. La synthese reduite d'acide retinoique est un mecanisme candidat interessant car il est implique dans le controle de la reprogrammation epigenetique et l'engagement vers un lignage cellulaire particulier, processus qui peuvent avoir des consequences indesirables dans la formation du placenta et, subsequemment, dans la programmation foetale. [Traduit par la Redaction] Mots-cles : ethanol, programmation, embryon, epigenetique, acide retinoique.
Introduction It is well established that the period around conception is a 'critical window' during development, in which suboptimal conditions can result in the programming of adult disease (Kwong et [...]