Independent and Combined Effects of Bisphenol A and Diethylhexyl Phthalate on Gestational Outcomes and Offspring Development in Sprague‐Dawley Rats

Abstract

Background Bisphenol A (BPA) and Diethylhexyl Phthalate (DEHP) are common plastic‐derived environmental contaminants that act as endocrine disrupting chemicals (EDCs) and pose risks for expecting mothers and offspring. Research addressing the effect of a mixture of these EDCs is limited. Objective To assess the sex‐specific consequences of developmental exposure to individual as well as mixtures of environmentally relevant doses of BPA/DEHP in male and female Sprague‐Dawley rats. Methods From gestational day 6 till 21, dams were orally administered either saline (control), BPA (5mg/Kg BW/day), low‐dose (LD) DEHP (5mg/Kg BW/day), high‐dose (HD) DEHP (7.5 mg/Kg BW/day), a combination of BPA and LD DEHP (B+LD‐D), or a combination of BPA and HD DEHP (B+HD‐D). Gestational weights and number of abortions were tracked. Litter size and weights, number of live births and stillbirths were counted. Morphometric parameters at birth were measured. Body weighs, food and water intakes were monitored weekly from postnatal weeks 3–12. Male and female offspring were sacrificed at 16–24 weeks of age and organs were dissected and weighed. Results The abortion rate of dams exposed to HD DEHP and the mixtures, B+LD‐D and B+HD‐D were higher at 8, 14 and 23% respectively. Gestational index was reduced in these groups as well. Prenatal exposure to BPA or HD DEHP significantly decreased relative thymus weight in male but not female offspring at 16 weeks. Relative heart weight increased in B+HD‐D exposed male offspring compared to the other groups. No programming effects in relative organs weights were detected in female offspring. Conclusion The results indicate that a mixture of BPA and DEHP, even at low doses, induced a pronounced effect on pregnancy outcomes. Male offspring appear to be more susceptible to the programming effects of these EDCs or their mixture. This suggests a great need to reconsider the possible additive, antagonistic or synergistic effects of EDC mixtures to which pregnant individuals are commonly exposed to. Support or Funding Information Supported by UGA research foundation.