Perinatal Combinational Exposure to Bisphenol A and a High-Fat Diet Contributes to Transgenerational Dysregulation of Cardiovascular and Metabolic Systems in Mice

Juncheng Liu; Maolin Liao; Rongfeng Huang; Yuehua You; Xiaojing Lin; Hong Yang; Lei Fan; Ying Zhong; Xinyu Li; Jibin Li; Xiaoqiu Xiao

doi:10.3389/fcell.2022.834346

Perinatal Combinational Exposure to Bisphenol A and a High-Fat Diet Contributes to Transgenerational Dysregulation of Cardiovascular and Metabolic Systems in Mice

Front Cell Dev Biol. 2022 Feb 24:10:834346. doi: 10.3389/fcell.2022.834346. eCollection 2022.

Authors

Juncheng Liu^{1

2}, Maolin Liao², Rongfeng Huang², Yuehua You^{1

2}, Xiaojing Lin², Hong Yang^{1

2}, Lei Fan², Ying Zhong^{2

3}, Xinyu Li^{2

4}, Jibin Li³, Xiaoqiu Xiao^{1

2}

Affiliations

¹ Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
² The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
³ Department of Nutrition and Food Hygiene, School of Public Health and Management, Chongqing Medical University, Chongqing, China.
⁴ Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

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.

Keywords: bisphenol A; cardiovascular system; obesity; offspring; transgenerational inheritance.