Epigenetics of sexual dimorphism under different maternal diets in mouse placenta
Résumé
The recent and rapid worldwide increase in noncommunicable diseases challenges the assumption that genetic factors are the primary contributors tc such diseases. A new dimension, thalof the "developmental origins of health and disease" (DOHaD), is at stake and therefore requires a paradigm shift. Maternai obesity and malnutrition p1*edispose 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. Placenta is a programming agent of aduheah and diseases. Adaptation in placenta! phenotype in response tc maternai diet and body composition alter fetal nutrient provision. This implies important epigenetic changes that are however still poorly documented in DOHaD studies, particularly concerning overnutrition. 0ur objective was tc investigate the effects of a high fat diet (HFD) on meuse placenta! development. We used transcriptomic and epigenetic techniques and showed for the first time that not onlythe gene sets but aIso the biological functions affected by the HFD differed markedly between the two sexes. Moreove1*, the expression of the epigenetic machinery enzymes, as weil as global DNA methylabon, were highly dynamic during the fetal period (3 stages), clearly differed between the 2 layers of placenta (labyrinth and junctional zone) and showed conspicuous sexual dimorphism. Thus, these findings demonstrate a striking sexual dimorphism of programming trajectories in response to the same environmental challenge. Explaining the sex-specific causal variables and how males versus females respond and adapt to environmental perturbations should help physiciens and patients an1icipate disease susceptibility.