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Neuroendocrine disruption by bisphenol A and/or di(2-ethylhexyl) phthalate after prenatal, early postnatal and lactational exposure

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Abstract

Bisphenol A (BPA) and di(2-ethylhexyl)phthalate (DEHP) are abundant endocrine disrupting chemicals (EDCs). In recent years, studies showed that EDCs may lead to neurodevelopmental diseases. The effects of prenatal exposure to these chemicals may have serious consequences. Moreover, exposure to EDCs as a mixture may have different effects than individual exposures. The present study aimed to determine the toxicity of BPA and/or DEHP on central nervous system (CNS) and neuroendocrine system in prenatal and lactational period in Sprague-Dawley rats. Pregnant rats were randomly divided into four groups: control (received vehicle); BPA group (received BPA at 50 mg/kg/day); DEHP group (received DEHP at 30 mg/kg/day); and combined exposure group (received both BPA at 50 mg/kg/day and DEHP at 30 mg/kg/day) during pregnancy and lactation by oral gavage. At the end of lactation, male offspring (n = 6) were randomly grouped. The alterations in the brain histopathology, neurotransmitter levels and enzyme activities in the cerebrum region, oxidative stress markers, and apoptotic effects in the hippocampus region were determined at adulthood. The results showed that exposure to EDCs at early stages of life caused significant changes in lipid peroxidation, total GSH and neurotransmitter levels, and activities of neurotransmitter-related enzymes. Moreover, BPA and/or DEHP led to apoptosis and histopathologic alterations in the hippocampus. Therefore, we can suggest that changes in oxidant/antioxidant status, as well as in neurotransmitters and related enzymes, can be considered as the underlying neurotoxicity mechanisms of BPA and DEHP. However, more mechanistic studies are needed.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was supported by Hacettepe University Scientific Projects Coordination Unit [Project no: TYL-2018-17006].

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Authors and Affiliations

  1. Faculty of Pharmacy, Department of Toxicology, Hacettepe University, Ankara, Turkey

    Anil Yirun, Gizem Ozkemahli, Aylin Balci & Pinar Erkekoglu

  2. Faculty of Pharmacy, Department of Toxicology, Çukurova University, Adana, Turkey

    Anil Yirun

  3. Faculty of Pharmacy, Department of Toxicology, Erzincan Binali Yildirim University, Erzincan, Turkey

    Gizem Ozkemahli

  4. Faculty of Medicine, Department of Histology and Embryology, Hacettepe University, Ankara, Turkey

    Naciye Dilara Zeybek & Nilgun Yersal

  5. Faculty of Pharmacy, Department of Toxicology, Lokman Hekim University, Ankara, Turkey

    Belma Kocer-Gumusel

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  1. Anil Yirun
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  2. Gizem Ozkemahli
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  3. Aylin Balci
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  4. Pinar Erkekoglu
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  7. Belma Kocer-Gumusel
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Contributions

AY performed tissue preparation, measurement of neuroendocrine parameters and oxidative stress parameters, and TUNEL assay. GO performed dosing and euthanasia of animals, tissue preparation, and measurement of neuroendocrine parameters. AB performed dosing and euthanasia of animals and measurement of oxidative stress parameters. PE performed study conception and design, euthanasia of animals, tissue preparation, statistical analyses, and evaluation of results. NY performed histopathological examinations and TUNEL assay. NDZ performed histopathological examinations and TUNEL assay. BKG performed study conception and design, statistical analyses, evaluation of results, and was a major contributor in writing the manuscript. All authors read and approved the final manuscript.

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Correspondence to Belma Kocer-Gumusel.

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The authors declare that they have no conflicts of interest.

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The study was approved by Gazi University Animal Ethics Committee (G.U.ET–18.043).

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Yirun, A., Ozkemahli, G., Balci, A. et al. Neuroendocrine disruption by bisphenol A and/or di(2-ethylhexyl) phthalate after prenatal, early postnatal and lactational exposure. Environ Sci Pollut Res 28, 26961–26974 (2021). https://doi.org/10.1007/s11356-021-12408-9

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  • DOI: https://doi.org/10.1007/s11356-021-12408-9

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