Early development and impacts on health and disease risk

In recent decades the social and economic impacts of rising rates of chronic disease states, including obesity, diabetes, and cardiovascular disease, have prompted a global investigation into their causes as well as their consequences. Though initially considered to be largely determined by genetic and lifestyle factors, this paradigm would ultimately be insufficient to explain the continued propagation of non-communicable diseases. It is now established that perturbations during critical developmental windows result in (mal)adaptations that confer long-term disease risk, rather than health. Experimental and clinical studies have been essential in defining the nature and extent to which parental diet and metabolic status have on the developing fetus. In our work, we investigate how periconceptional nutritional adversity impacts maternal-fetal-placental relationships and impairs offspring reproductive and metabolic function. We show that maternal diet-induced obesity modifies maternal gut microbial communities, which may impact maternal metabolism through altered production of bacterial metabolites, including short-chain fatty acids (SCFAs) increasing intestinal permeability and altering maternal immune function. We show that paternal diet also participates in fetoplacental growth and development and influences placental development and in turn impairs offspring metabolic function. Regardless of the initiating lineage, an adverse in utero environment fuels changes in fetoplacental development and function, ultimately leading altered physiological function in the offspring long term.