Effects of the Use of Assisted Reproductive Technologies and an Obesogenic Environment on Resistance Artery Function and Diabetes Biomarkers in Mice Offspring

Abstract

Maternal obesity affects the incidence of cardiovascular disease and diabetes in offspring. Also the use of assisted reproductive technologies (ART) has been associated with cardiovascular deficiencies in offspring. Obese women often suffer from infertility and use ART to achieve a pregnancy, but the combined effects of maternal obesity and ART on cardiovascular health and incidence of diabetes in the offspring is not known. Here, we report the effects of the use of ART within an obesogenic environment, consisting of feeding a western diet (WD) to dams and offspring, on resistance artery function and presence of diabetes biomarkers in juvenile mice offspring. Our results indicate that WD and ART interacted to induce endothelial dysfunction in mesenteric resistance arteries isolated from 7-week-old mice offspring. This was determined by presence of a reduced acetylcholine-induced dilation compared to controls. The arteries from these WD-ART mice also had greater wall cross-sectional areas and wall to lumen ratios indicative of vascular hypertrophic remodeling. Of the diabetes biomarkers measured, only resistin was affected by a WD×ART interaction. Serum resistin was significantly greater in WD-ART offspring compared to controls. Diet and sex effects were observed in other diabetes biomarkers. Our conclusion is that in mice the use of ART within an obesogenic environment interacts to favor the development of endothelial dysfunction in the resistance arteries of juvenile offspring, while having marginal effects on diabetes biomarkers.

Maternal Hyperleptinemia Is Associated with Male Offspring’s Altered Vascular Function and Structure in Mice

“…This is supportive of the hypothesis that alterations in maternal serum leptin may contribute to the changes in cardiovascular health observed in offspring of obese or diabetic pregnancies. This study also strengthens the idea that programming of arterial function may precede changes in blood pressure, and thus, may be a key mechanism by which maternal environment can alter cardiovascular health [ 40 , 53 ]. While alterations to vascular function are linked to the development of hypertension, it is important to note that these changes appear to occur prior to the onset of hypertension and that multiple vascular changes are observed in multiple vascular beds.…”

“…Exposure to an adverse maternal environment also can lead to the development of hypertension and CVD [ 50 – 52 ]. However, there is limited information on the role that alterations in resistance artery function and structure play in programming of hypertension by the maternal environment [ 4 – 7 , 40 , 53 ]. In the offspring of hyperleptinemic dams, differences in resistance artery function were present without hypertension or obesity in the offspring suggesting first, that differences in resistance artery function and structure were directly programmed in utero , rather than resulting secondarily from differences in blood pressure or metabolism in the offspring.…”

Endothelial Mineralocorticoid Receptor Mediates Diet-Induced Aortic Stiffness in Females

“…3 Mesenteric resistance arteries were isolated and cannulated onto glass micropipettes, pressurized at 70 mmHg without flow, and warmed to 37°C in commercial pressure myograph chambers (Living Systems Instrumentation, Burlington, VT, USA) as previously described. 3, 19, 20 …”

Can assisted reproductive technologies cause adult-onset disease? Evidence from human and mouse

“…Donjacour et al demonstrated reduced systolic blood pressure and enlarged left heart in male mice produced after IVF and suboptimal embryo culture conditions [56]. In contrast, blood pressure changes were not observed in a different study that also targeted embryo culture procedures [57,58]. However, under high fat diet conditions, mice produced from superovulation and subsequent culture of embryos that were fertilized in vivo exhibited impaired endothelial-dependent artery vasodilation and vasculature structural changes [58].…”

“…In contrast, blood pressure changes were not observed in a different study that also targeted embryo culture procedures [57,58]. However, under high fat diet conditions, mice produced from superovulation and subsequent culture of embryos that were fertilized in vivo exhibited impaired endothelial-dependent artery vasodilation and vasculature structural changes [58]. Taken together, these studies demonstrate that ART in the mouse appropriately models the postnatal cardiovascular dysfunction observed in humans and has provided experimental evidence that culture conditions may be the source of adverse effects contributing to cardiac dysfunction in offspring.…”