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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Neuroendocrine Science
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1479838
This article is part of the Research Topic Effects of Prenatal Exposure to Endocrine-Disrupting Chemicals View all 6 articles

Prenatal Bisphenol A and/or Diethylhexyl Phthalate exposure followed by adult estradiol treatment affects behavior and brain monoamines in female rat offspring

Provisionally accepted
Amrita Kaimal Amrita Kaimal 1Jessica M Hooversmith Jessica M Hooversmith 1Maryam H Al Mansi Maryam H Al Mansi 2Ariana D Cherry Ariana D Cherry 2Jillian T Garrity Jillian T Garrity 2Philip Holmes Philip Holmes 1Puliyur S MohanKumar Puliyur S MohanKumar 1,2Sheba MJ MohanKumar Sheba MJ MohanKumar 1,2,3*
  • 1 Neuroscience Division, Biomedical Health Sciences Institute, University of Georgia, Athens, Georgia, United States
  • 2 Department of Biomedical Sciences, College of Veterinary Medicine, University of Georgia, Athens, United States
  • 3 University of Georgia, Athens, United States

The final, formatted version of the article will be published soon.

    Women are at increased risk for mood disorders, which may be partly attributed to exposure to endocrine-disrupting chemicals (EDCs) during sensitive periods such as pregnancy. Exposure during these times can impact brain development in the offspring, potentially leading to mood disorders in later life. Additionally, fluctuating levels of endogenous estrogens, as seen during pregnancy, or the use of oral contraceptives, can further elevate this risk. This study examines the cumulative effects of prenatal EDC exposure combined with chronic low-dose 17β-estradiol (E2) treatment in adulthood on neurobehavioral outcomes. Pregnant Sprague-Dawley rats were orally dosed with vehicle, bisphenol A (BPA) (5 µg/kg body weight (BW)/day), low-dose (LD) diethylhexyl phthalate (DEHP) (5 µg/kg BW/day), high-dose (HD) DEHP (7.5 mg/kg BW/day), or a combination of the two (BPA+DEHP) from gestational days 6-21. At 3 months of age, female offspring were implanted with slow-release E2 pellets or were sham-implanted. Following a 90-day treatment period, behavioral testing was conducted, and serum hormones and brain monoamine levels were analyzed. Chronic E2 treatment in controls increased anxiety and reduced active coping behaviors. In DEHP- and BPA+DEHP-exposed offspring, E2 treatment reversed some of these effects. Dose-dependent alterations in circulating hormone levels and brain monoamines were observed. Dysregulation of the stress axis was particularly notable with the higher dose of DEHP. Overall, prenatal EDC exposure altered behavior, hormones, and brain monoamines, with adult E2 treatment further exacerbating some of these effects in female offspring.

    Keywords: bisphenol A (BPA), Diethylhexyl phthalate (DEHP), Prenatal exposure, Behavior, monoamine neurotransmitters, endocrine-disrupting chemical (EDC) mixtures

    Received: 12 Aug 2024; Accepted: 25 Nov 2024.

    Copyright: © 2024 Kaimal, Hooversmith, Al Mansi, Cherry, Garrity, Holmes, MohanKumar and MohanKumar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Sheba MJ MohanKumar, University of Georgia, Athens, United States

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