Bisphenol-S Exposure Exacerbates Aortic Stiffening in a Model of Early Life Stress

Early life stress (ELS) poses a significant burden to public health. As many as two-thirds of individuals in the US experience at least one adverse childhood experience or early life stressor. These stressors lead to poorer health outcomes later in life including an increased risk for developing cardiovascular disease (CVD). Previous research demonstrates that ELS leads to an increase in vascular superoxide production and endothelial dysfunction as well as marked increases in pulse wave velocity (PWV), a measure of arterial stiffness and a predictor of the development of CVD. However, it is important to consider that ELS does not happen in isolation. Individuals with higher ELS exposure are also exposed to additional stressors, including environmental exposures. Bisphenol S (BPS), a common component of plastics, is an analog of bisphenol A (BPA) and has begun to replace BPA in many products including baby bottles, receipt coatings, and food containers. Individuals are frequently exposed through food, drink and transdermal absorption. Recent work demonstrates that exposure to BPS at low levels in the drinking water results in increased oxidative stress and endothelial dysfunction. We hypothesized that exposure to both ELS and BPS will result in a greater risk for developing CVD. Maternal separation with early weaning (MSEW) was used to model ELS. In MSEW, pups are separated from the dam 4h/day (postnatal day (PD) 2 to PD5), 8h/day (PD6 to 16), and weaned at PD17. Normally reared controls (NR) remain undisturbed with the dam until standard weaning at PD21. At PD21, weaned male MSEW and NR received a low concentration of BPS (250 nM) or vehicle in the drinking water in glass containers until 12 weeks of age. Water volume consumed per day and body weight at time of sacrifice were recorded and no differences were observed between groups. PWV was measured at 11 weeks of age. We found that MSEW mice receiving vehicle and NR mice that received BPS water had significantly increased PWV as compared to NR control mice on vehicle drinking water (mm/sec; MSEW+Vehicle: 2.04±0.07, NR+BPS: 2.01±0.09, NR+Vehicle: 1.39±0.06, p=0.00003, p<0.0001, n=7,9,5). Moreover, MSEW mice that received BPS in their drinking water had significantly higher PWV as compared to both MSEW with vehicle and NR mice with BPS water indicating a compounding effect of stress and BPS exposure (mm/sec; MSEW+BPS: 3.07±0.08, MSEW+Vehicle: 2.04±0.07, NR+BPS: 2.01±0.09; p<0.0001; n=7,7,9). Histological analysis of aortae from all mice at 12 weeks of age revealed no significant differences in wall thickness. These data demonstrate that exposure to early life stress may increase development of CVD risk when exposed to BPS in daily life. NIH P01 HL158500, T32GM135028 & R25 DK 112731 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.