Combined Exposure to Endocrine Disruptors, BPA and BP-3, during Pregnancy and Lactation Alters Postnatal Body Mass, Growth, White Adipose Tissue Morphology, and Adipogenic Gene Expression in a Sex-Specific Manner

Endocrine-disrupting chemicals (EDCs) like bisphenol A (BPA) and benzophenone-3 (BP-3) are omnipresent and previously linked to various metabolic disorders. As EDC exposure already begins during prenatal development, we investigated the effects of BPA and BP-3 exposure during gestation and lactation using a murine model on adipogenesis and metabolic pathways in white adipose tissue (WAT) in the offspring. We monitored postnatal body mass and analyzed the morphology and gene expression of WAT in adult male and female offspring. BPA- and BPA+BP-3-exposed males showed an increase in body mass in early adulthood, whereas BP-3-exposed females presented a decreased growth rate later in life. We identified altered adipocyte area and distribution, suggesting hyperplasia in the WAT of BPA and BPA+BP-3-exposed males. Gene expression analysis showed Pparg upregulation in BPA+BP-3-exposed males and Fabp4 and Adipoq downregulation in BP-3-exposed females. Sex-specific associations between gene expression, adipocyte area, and body mass in controls were disrupted by EDC exposure. Our findings suggest increased postnatal body mass and Pparg-mediated WAT hyperplasia in BPA+BP-3-exposed male mice. Fabp4 and Adipoq downregulation may be responsible for counteracting the BP-3-induced metabolic dysregulation in females. This calls for consideration of sex-specific differences of endocrine disruption in the future development of preventive and therapeutic targets for metabolic disorders.