Sex differences in the developmental origins of cardiometabolic disease following exposure to maternal obesity and gestational diabetes 1 .

Over the past 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 of gestational diabetes mellitus (GDM). It is increasingly accepted by the scientific community that 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 theory. Evidence from human cohorts and epidemiological and animal studies has shown that maternal obesity and GDM condition the offspring for cardiometabolic disease development. These effects are most likely regulated by epigenetic mechanisms; however, biological sex is an important factor in defining the risk of the development of several metabolic health disorders. The aim of this review is to describe the 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. In addition, this review addresses 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 in the development of effective therapeutic strategies for the treatment of cardiometabolic diseases that exhibit sexual dimorphism.