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Conference Papers Year : 2023

Effects of maternal obesity on offspring health: implication of the histone aceylation pathway


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. 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 and olfactory behavioral trajectories. After only few weeks of HFD, the offspring developed obesity, metabolic alterations and olfactory impairments, 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 but had a reduction in olfactory sensitivity, along with a lack of fasting-induced, olfactory-based motivation. 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 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. This study highlights the high sensitivity of the epigenetic machinery gene expression, and particularly the histone acetylation pathway, to maternal obesity. Preconceptional weight loss appears beneficial to fetal growth, but induces some possible adverse outcomes on olfactory-based behaviors. These obesity-induced transcriptional changes could alter the placental and the hepatic epigenome, leading to FGR. We are currently developing methodologies to study the whole genome histone acetylation profile on snap-frozen tissue from this project biobank.
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Dates and versions

hal-04143096 , version 1 (27-06-2023)


  • HAL Id : hal-04143096 , version 1


Anne Gabory. Effects of maternal obesity on offspring health: implication of the histone aceylation pathway. Advances in Epigenetics, Active Motif; Amélie Bonnet-Garnier, Apr 2023, Jouy-En-Josas, France. ⟨hal-04143096⟩
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