Abstract
Bisphenol A (BPA) is a major environmental pollutant and food contaminant with endocrine-disrupting effects on human and animal health. Perinatal and developmental exposure to BPA has been known to cause hepatotoxicity in adulthood. However, its intergenerational effects in a metabolically challenged population have been scarcely investigated. Our study was designed to assess the intergenerational effect of an environmentally relevant dose of BPA and diet-induced parental obesity on the hepatic health outcome of F1 offspring. Wistar rats were given a high-fat diet to induce obesity, followed by chronic low dosages of BPA (10 ppm × 180 days) in drinking water. Post-treatment, rats were crossed within groups to obtain the F1 generation. Weanling pups were observed for weight gain, levels of hepatic antioxidants, liver function enzymes, cholesterol, C-reactive protein, and triglyceride in the serum. Histological changes in the liver tissue were also investigated. mRNA expression of energy homeostasis genes (FTO and MCR-4) in the liver was analyzed alongside blood biomarkers. We observed higher birth weight and rapid weight gain in the test group in comparison with controls, which was consistent with the changes in mRNA and protein expression of FTO and MCR-4. BPA caused a significant, treatment-related change in the inflammatory marker C-reactive protein, lipid peroxidation, antioxidants, and lipid profile. These findings were accompanied by histological changes in the liver tissue characteristic of hepatic steatosis indicating the onset of the non-alcoholic fatty liver disease (NAFLD). Our study offers a link between exposure to BPA in parents and onset of NAFLD in their offspring.
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Dr. S.D. Sharma of the Central Instrumentation Facility, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, India, facilitated the use and troubleshooting of instruments. Dr. Wara Prasad, Veterinary Pathologist, facilitated the histopathological analysis of slides.
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The student fellowship and project grant was funded by University Grants Commission-Maulana Azad National Foundation (UGC-MANF- Grant #201516-MANF-2015-17-UTT-59439).
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S. Dabeer: conceptualization, methodology, investigation, writing — original draft, formal analysis, data curation; S. Raisuddin: conceptualization, supervision, funding acquisition, resources, data curation, project administration, writing — original draft and editing, formal analysis, data curation.
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Dabeer, S., Raisuddin, S. Perinatal exposure to environmental endocrine disruptor bisphenol A aggravates the onset of non-alcoholic fatty liver disease (NAFLD) in weanling F1 offspring of obese rats. Environ Sci Pollut Res 30, 3146–3165 (2023). https://doi.org/10.1007/s11356-022-22246-y
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DOI: https://doi.org/10.1007/s11356-022-22246-y