Dietary Phytoestrogens Do Not Alter Cardiovascular Function in Lean Intact and Ovariectomized Female Mice

In the last several years, there has been a preponderance of conflicting data enumerating the benefits as well as harmful effects of dietary phytoestrogens, which are plant-derived compounds found commonly in soybeans and containing isoflavones genistein and daidzein. Global trends for soybean consumption have risen sharply in foods, infant formulas, alternative milk options, and oils. While some reports demonstrate that dietary phytoestrogens can improve metabolic functions, especially in obese menopausal women, others have indicated that phytoestrogens can disrupt endocrine signaling. We aimed to test whether exogenous phytoestrogens provided in normal chow diet would alter vascular function and blood pressure (BP) in lean intact and ovariectomized female mice. Female C57BL/6 mice underwent either sham or ovariectomy (OVX) surgery at 12 weeks and were placed on either standard chow diet containing phytoestrogen (Teklad 2018, 150-340 mg/kg isoflavone content) or Phytoestrogen-free diet (AIN-76A purified diet, Teklad) with similar nutritional value. After 4 weeks of treatment, mice were euthanized, tissues were collected for qPCR, and conduit (thoracic aorta) and resistance (second order mesenteric) arteries were isolated for vascular studies. Uterine weight was measured to validate the efficacy of ovariectomy surgery. BP recording via tail cuff indicated that removal of endogenous estrogen production with OVX did not alter systolic BP. Additionally, the presence of phytoestrogens in the diet did not elicit changes in BP (2-way ANOVA, p>0.05) for either sham or OVX mice. Vascular function of mesenteric artery and thoracic aorta via wire myography indicated that neither OVX nor consumption of dietary phytoestrogens altered (2-way ANOVA, p>0.05) endothelial-dependent relaxation to acetylcholine (Ach), endothelial-independent relaxation to sodium nitroprusside (SNP), nor constriction to phenylephrine (Phe). In the absence of exogenous estrogens in the diet, OVX does not alter plasma leptin levels but dietary phytoestrogens significantly increased (2-way ANOVA, p<0.05) circulating leptin levels, with a trend for an even greater level in OVX mice. Removal of endogenous estrogen production via OVX does not alter adrenal aldosterone synthase (CYP11B2) but phytoestrogen in the diet increases adrenal CYP11B2 (2-way ANOVA, p<0.05) exclusively in sham mice. Surprisingly, the presence or absence of either endogenous or exogenous estrogens with OVX and diet, respectively, elicited no change in plasma aldosterone levels. These data suggest dietary phytoestrogens did not alter blood pressure, vascular function, or circulating aldosterone levels in lean ovariectomized mice. These findings indicate that in lean female mice, exogenous phytoestrogens consumed through the diet do not impact vascular function and blood pressure regulation in either cycling or ovariectomized female mice but promote leptin production, which may alter metabolic function. R01HL130301, R01HL155265 (E.J.B.) F31HL168963-01 (C.T.B.) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.