Files
Abstract
Humans are consistently exposed to the plastic-derived environmental contaminants Bisphenol A (BPA) and Diethyl-hexyl Phthalate (DEHP) that can act as endocrine-disrupting chemicals (EDCs). Given the evidenced mass production, chronic exposure, and detection of BPA and DEHP in most fetuses and adults, studies addressing their cumulative effect are needed. We, therefore, aimed to investigate how these chemicals, alone and in mixtures, interact at environmentally relevant doses to affect health; and how a high-fat diet (HFD) in adulthood can mediate these effects. We treated pregnant Sprague Dawley rats from gestational days 6-12 with individual and combinations of BPA and DEHP, at high (HD) or low (LD) doses. We further dissected the postnatal growth and metabolic trajectories in male and female offspring. We found that combinations of BPA and DEHP, even at low doses, reduced the ability of pregnant dams to maintain pregnancies, and altered offspring birth anthropometric parameters. Female offspring prenatally exposed to BPA+HD-DEHP mixture exhibited postnatal growth retardation, reduced food consumption, fluid retention, impaired fasting glucose, and an increase in liver cholesterol. In utero exposure to BPA, alone and when combined with HD-DEHP, compromised glucose homeostasis in male adults without altering their growth trajectory. No major effects were seen at low doses of individual EDCs; however, combined exposure to BPA+LD-DEHP coupled with HFD challenge in adulthood increased the abdominal and thoracic circumference of female offspring. In utero exposure also affected male immune and cardiovascular systems as indicated by premature thymus involution in BPA or HD-DEHP offspring and heart hypertrophy after BPA+HD-DEHP exposures. With growing health concerns about BPA, industries have switched to using BPA analogs, Bisphenol S and F (BPS and BPF), without any understanding of their health effects. We, therefore, examined the effects of prenatal exposure to BPA, BPS, and BPF on offspring’s growth and metabolic profile. Despite some evidence of obesity in BPF and BPS male offspring, no effects were seen in terms of glucose homeostasis.
By accounting for chemical mixtures and examining BPA substitutes, these studies identified previously undocumented sex-specific risk factors for growth and metabolic disorders that should be considered in the risk assessment process.