Abstract
BackgroundMaternal obesity impacts fetal growth and pregnancy outcomes. To counteract the deleterious effects of obesity on fertility and pregnancy issue, preconceptional weight loss is recommended to obese women. Whether this weight loss is beneficial/detrimental for offspring remains poorly explored. 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. We also tested whether preconceptional weight loss could alleviate these effects.ResultsFemale mice were fed either a control diet (CTRL group), a high-fat diet (obese (OB) group), or a high-fat diet switched to a control diet 2 months before conception (weight loss (WL) group). At mating, OB females presented an obese phenotype while WL females normalized metabolic parameters. At embryonic day 18.5 (E18.5), fetuses from OB females presented fetal growth restriction (FGR; −13 %) and 28 % of the fetuses were small for gestational age (SGA). Fetuses from WL females normalized this phenotype. The expression of 60 epigenetic machinery genes and 32 metabolic genes was measured in the fetal liver, placental labyrinth, and junctional zone. We revealed 23 genes altered by maternal weight trajectories in at least one of three tissues. The fetal liver and placental labyrinth were more responsive to maternal obesity than junctional zone. One third (18/60) 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 (13/18). 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.ConclusionsThis study highlights the high sensitivity of the epigenetic machinery gene expression, and particularly the histone acetylation pathway, to maternal obesity. These obesity-induced transcriptional changes could alter the placental and the hepatic epigenome, leading to FGR. Preconceptional weight loss appears beneficial to fetal growth, but some effects of previous obesity were retained in offspring phenotype.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0188-3) contains supplementary material, which is available to authorized users.
Highlights
Maternal obesity impacts fetal growth and pregnancy outcomes
We showed that maternal obesity induced fetal growth restriction (FGR), which was associated with an altered expression of histone acetylation modifiers in the fetal liver and labyrinth, but not in the junctional zone
We showed that the expression of hydroxysteroid 11beta dehydrogenase 1 (Hsd11β1), insulin receptor substrate 1 (Irs1), and tryptophan hydroxylase 1 (Tph1) was downregulated in the placental labyrinth of obese females (OB) dams (Table 1, Fig. 6b–d)
Summary
To counteract the deleterious effects of obesity on fertility and pregnancy issue, preconceptional weight loss is recommended to obese women. Whether this weight loss is beneficial/detrimental for offspring remains poorly explored. FGR is associated with a high incidence of metabolic diseases in adulthood [7, 8], which is consistent with the developmental origins of health and disease (DOHaD) concept. This concept, named “developmental programming” or “conditioning,” states that environmental factors during early development could predispose an individual to chronic diseases [9]
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