The effects of dietary soy content on cerebral artery function and behavior in ovariectomized female mice

Abstract

Introduction: As females age, they transition through menopause, experiencing a decrease in estrogen and an increase in cardiovascular and neurodegenerative disease risk. Most standard rodent chows contain phytoestrogen-rich soybean meal, which mimic the effects of estrogen. Understanding the impact of soybean meal on vascular outcomes is crucial to proper experimental design. Thus, this study aimed to compare the effects of standard and soy-free chows on cerebral artery endothelial function and cognitive function in ovariectomized mice. Methods: Young female C57Bl/6J mice (n=43; ~6 mo) were randomly assigned to 3 groups: Sham, ovariectomy (OVX), or ovariectomy on a diet containing soy (OVX+Soy). Results: In posterior cerebral arteries, OVX mice had a 27% lower maximal response to insulin compared with the Sham mice. The OVX+Soy mice had a 27% greater maximal vasodilation to insulin compared with the OVX mice and there were no differences in vasodilation between the OVX+Soy and Sham groups. The group differences in vasodilation were mediated by differences in nitric oxide bioavailability. The OVX+Soy mice also had greater insulin receptor gene expression in cerebral arteries compared with the OVX mice. However, no differences in aortic or cerebral artery stiffness were observed between groups. Interestingly, the OVX+Soy group scored better on nesting behavior compared with both Sham and OVX groups. Conclusion: In summary, we found that ovariectomy impairs insulin-mediated vasodilation in cerebral arteries, but a diet containing soy mitigates these effects. These findings highlight the importance of considering dietary soy when performing vascular and behavioral tests in mice, particularly in females.