Maternal diets trigger sex-specific divergent trajectories of gene expression and epigenetic systems in mouse placenta

National audienceThere is mounting evidence that placenta can be considered as a programming agent of adult health and diseases.1 Placental weight and shape at term are correlated with the development of metabolic diseases in adulthood in humans. Maternal obesity and malnutrition predispose the offspring to develop metabolic syndrome, a vicious cycle leading to transmission to subsequent generation(s), with differences in response and susceptibility according to the sex of the individual. Adaptations in placental phenotype in response to maternal diet and body composition alter fetal nutrient provision. This implies important epigenetic changes.2 However, the epigenetics of placental development in DOHaD studies is still poorly documented, particularly concerning overnutrition. We used histology, microarray analysis and epigenetic techniques to investigate the effects of a high-fat diet (HFD) on mouse development. We showed for the first time that not only the gene sets but also their biological functions affected by the HFD differed markedly between the two sexes. Remarkably, genes of the epigenetic machinery and global DNA methylation levels showed sexual dimorphism. Imprinted gene expression was altered, with locus-specific changes in DNA methylation. Thus, these findings3,4 demonstrate a striking sexual dimorphism of programming trajectories in response to the same environ- mental challenge. Explaining the sex-specific causal variables and how males v. females respond and adapt to environmental perturbations should help physicians and patients anticipate disease susceptibility