Sex differences in the developmental origins of cardiometabolic disease following exposure to maternal obesity and gestational diabetes.

Over the last 30 years, the worldwide prevalence of obesity has nearly doubled. In addition, more and more women in their child bearing years are overweight or obese, which increases the risk for gestational diabetes mellitus (GDM). It is increasingly accepted by the scientific community that the early life exposure to environmental stress influences the long-term health of an individual, which has been termed the Developmental Origins of Health and Disease (DOHaD) theory. Evidence from human cohorts, epidemiological and animal studies have reported that maternal obesity and GDM alter the epigenome of the next generation, conditioning the offspring for cardiometabolic disease development. These effects are most likely regulated by epigenetic mechanisms; however, biological sex is an important factor in defining risk for the development of several metabolic health disorders. The aim of this review is to describe current evidence from human cohort and animal model studies that implicates sex differences in the developmental origins of cardiometabolic disease following exposure to maternal obesity and GDM. Additionally, this review will address the potential mechanisms involved in these sex differences. In many studies, sex is ignored as an important variable in disease development; however, the results presented in this review highlight important differences between sexes in the developmental programming of biological responses to exposures during the fetal stage. This knowledge will ultimately help for the development of effective therapeutic strategies for the treatment of cardiometabolic diseases that exhibit sexual dimorphism.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author