Effects of preconceptional maternal weight trajectories on offspring health

Since the 90’s, obesity became pandemic. Nutritional environment has an important impact during development, leading to the later onset of non-communicable diseases. Maternal environment may affect offspring development through epigenetic mechanisms, regulating gene expression and microbiota, which is a major actor of metabolism. In order to reduce fertility troubles and obstetrical complications caused by obesity, it is now recommended for women who plan a pregnancy to lose weight before conception. However, the long-term effects of this preconception weight loss are not well described in the literature. We aim to identify whether maternal weight loss prior to conception can prevent the development of metabolic syndrome at the adult age. We previously highlighted in a mouse model the high sensitivity of the epigenetic machinery gene expression, and particularly histone acetylation pathway, to maternal obesity. Preconceptional weight loss appears beneficial for fetal growth, but some effects of previous obesity were retained in offspring transcriptome. During my PhD, I will precise:- the offspring phenotype using metabolomics of adult liver, olfactory bulb and hypothalamus (LC-HRMS),- the epigenomic analysis by an histone acetylation study in fetal liver (ChIP-seq,- the microbiota component with an analysis of maternal and offspring gut microbiota (16S rRNA-seq).The correlation of metabolic parameters, epigenomic state and gut microbiota will give us information about the mechanisms of maternal diet’s effects and their participation to adult health conditioning