The impact of adverse maternal environments on resistance artery function and mechanical characteristics in offspring

Abstract

Cardiovascular disease is one of the leading causes of death worldwide. Maternal obesity, gestational diabetes mellitus (GMD) and assisted reproductive technologies (ART) have been associated with cardiovascular deficiencies in offspring. Obese women often suffer from infertility and use ART to achieve a pregnancy. Children of mothers that undergo ART or experience GDM have a higher risk of developing hypertension, but little is known about the mechanisms that control this process. Here, I report that in offspring, the interaction between a high fructose and high fat diet (also known as western diet, WD) and ART exhibited impaired endothelialdependent dysfunction in mesenteric resistance arteries, this was determined by the presence of reduced acetylcholine vasodilation. Arteries from WD-ART male mice had greater wall cross-sectional area (CSA) and wall-to-lumen ratio (W/L) compared to their respective ART control, indicative of vascular hypertrophic remodeling. Another adverse maternal environment during pregnancy is GDM, with 2-10 [percent] of pregnancies in the US being affected. To study this model, we designed a two-by-two experiment array using male mice, with main effects genotype and diet. In resistance mesenteric arteries of wild type (WT) offspring fed a WD experienced enhanced vasodilation to acetylcholine. Furthermore, in offspring of hyperleptinemic dams WD reduced vasodilation to insulin. Offspring of hyperleptinemic dams had stiffer arteries regardless of the diet. Therefore, we conclude that while maternal hyperleptinemia was beneficial to offspring vascular health fed a standard diet (SD), it had detrimental effects when fed a WD. The results of these two projects suggest that an adverse maternal environment (i.e. ART or GDM) in combination with a WD favors the development of endothelial dysfunction and arterial stiffening in resistance mesenteric arteries of offspring.