Effects of maternal obesity on offspring health: implication of the histone acetylation pathway | : Effets de l'obésité maternelle sur la santé de la descendance : implication de la voie d'acétylation des histones

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English. Introduction. According to the “developmental origins of health and disease” (DOHaD) concept, maternal obesity predisposes the offspring to non-communicable diseases in adulthood. Epigenetic mechanisms could be affected by maternal weight changes, perturbing expression of key developmental genes in the placenta or fetus. Our aim was to investigate the effects of chronic maternal obesity on feto-placental growth along with the underlying epigenetic mechanisms. Moreover, while a preconceptional weight loss (WL) is recommended for obese women, its benefits on the offspring have been poorly addressed. We therefore tested whether preconceptional weight loss could alleviate these effects.Materials and Results. At embryonic day 18.5 (E18.5), fetuses from obese females (OB group) presented fetal growth restriction. After weaning, the offspring were either put on a control diet (CD) or a high-fat (HFD) and we tracked their metabolic trajectories until adulthood. After only few weeks of HFD, the offspring developed obesity and metabolic alterations, independently of maternal context. However, male offspring born to obese mother gained even more weight under HFD than their counterparts born to lean mothers. Preconceptional WL normalized the offspring growth and metabolic phenotypes. We measured the expression of 60 epigenetic machinery genes and 32 metabolic genes in the fetal liver, placental labyrinth and junctional zone. One third of the epigenetic machinery genes were differentially expressed between at least two maternal groups. Interestingly, genes encoding proteins involved in the histone acetylation pathway were particularly altered. In OB group, lysine acetyltransferases and Bromodomain-containing protein 2 were upregulated, while most histone deacetylases were downregulated. In WL group, the expression of only a subset of these genes was normalized.Conclusion. This study highlights the high sensitivity of the epigenetic machinery gene expression, and particularly the histone acetylation pathway, to maternal obesity. Obesity-induced transcriptional changes could alter the placental and the hepatic epigenome. Preconceptional weight loss appears beneficial to fetal growth and offspring phenotype, but some possible adverse outcomes may persist. The whole genome histone acetylation profile is under study.