Abstract
Both bisphenol A (BPA) and high-fat diet (HFD) exert unfavorable effects on animals and humans; moreover, they could affect the health of their offspring. BPA and HFD often coexist in modern lifestyles; however, the long-term effects of simultaneous exposure of mothers to BPA and HFD during the perinatal period on the cardiovascular and metabolic systems of the offspring remain unclear. This study aimed to examine the effect of simultaneous exposure of mothers to BPA and HFD on the risk of metabolic and cardiovascular abnormalities in offspring. Institute of Cancer Research female mice (F0) were exposed to BPA and fed with HFD before and during gestation until the end of lactation. F0 mice were mated with untreated males to produce the first generation (F1); subsequently, adult F1 males/females were mated with normal females/males to produce the second generation (F2). Combined maternal exposure to BPA and HFD caused myocardial hypertrophy and aortic tunica media thickening as well as increased the cross-sectional area of cardiomyocytes and blood pressure in the matrilineal F2 generation. These cardiovascular changes might be associated with reduced endothelial nitric oxide synthase (eNOS) levels. The patrilineal female F2 was more likely to be obese than the patrilineal male F2. Re-feeding with a HFD showed a more significant weight gain and reduced energy expenditure. However, the aforementioned effects were not observed with exposure to HFD or BPA alone during the perinatal period. Our findings suggest that perinatal combinational exposure to BPA and HFD could cause metabolic and cardiovascular disorders in the offspring, Further, our findings demonstrate that the synergistic effects of HFD and BPA could be transmitted to future generations in a sex-dependent manner.