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Maternal obesity and preconceptional weight loss: high sensitivity of epigenetic regulators gene expression in relation to fetal growth and long-lasting effect in mice

Abstract : Maternal obesity impacts fetal growth and pregnancy outcomes. Epigenetic regulation, that stably modifies the phenotype through chemical changes within the chromatin without alteration in DNA sequence, is one of the potential mechanisms to memorize the parental environment, leading to disease in adulthood. To counteract the deleterious effects of obesity on fertility and pregnancy issues, preconceptional weight loss is recommencled to obese women. Whether this weight loss is beneficial or detrimental to the offspring remains poorly explored. Epigenetic mechanisms could be affected by maternal weight changes, perturbing expression of key devel­ opmental genes in the placenta or the fetus. Our aim was to investigate the effects of chronic maternal obesity on feto-placental growth at term of gestation and in adulthood, along with the underlying epigenetic mechanisms. We also testecl whether preconceptional weight loss could· alleviate these effects. Female mice were fed either a control diet (CTRL group), a high-fat diet (obese group, OB) for 4 months, or a high-fat diet switched to a control diet 2 months before conception (weight loss, WL) group). At mating, OB females exhibited an obese phenotype while WL females normalizecl their weight and metabolic parameters. At embryonic day 18.5, fetuses from OB females showed fetal growth restriction and the odd-ratio for small for gestational age phenotype (SGA) was 3.2. These parameters were normalized for WL fetuses. The expression of 60 epigenetic machinery genes and 32 metabolic genes was measured 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, especially the histone acetylation pathway. Maternal weight loss normalized the expression of only a subset of these genes. A second cohort of offspring was followed from birth until 6 months for weight gain, food intake, glucose metabolism and cholesterol. During lactation, OB offspring rapidly caught up in weight and after weaning the diet-induced obesity was enhanced in OB males compared to CTRL. No obvious phenotype was observed in female offspring. Maternal weight loss rescued this phenotype. These results show that expression of epigenetic machinery genes and in particular histone acety­ lation regulators, is highly sensitive to preconceptional maternal metabolic features. The obesity­ induced transcriptional changes could alter the placental and hepatic epigenomes, contributing to SGA phenotype. Preconceptional weight loss alleviates the effects of obesity on fetal and adult weight but even if obesity was cured before conception, some effects were retained in the offspring phenotype at term. This study is an important step toward understanding immediate and long-term mechanisms linking maternal nutrition to fetal growth and adult health
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  • HAL Id : hal-02741277, version 1
  • PRODINRA : 382194



Polina Panchenko, Sarah Voisin, Mélanie Jouin, Luc Jouneau, Marie-Christine Lacroix, et al.. Maternal obesity and preconceptional weight loss: high sensitivity of epigenetic regulators gene expression in relation to fetal growth and long-lasting effect in mice. 3. congrès de la SF-DOHaD, Société Francophone-DOHaD. FRA., Dec 2016, Paris, France. 84 p. ⟨hal-02741277⟩



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