Combined effects of di (2-ethylhexyl) phthalate and bisphenol A on thyroid hormone homeostasis in adolescent female rats
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RESEARCH ARTICLE
Combined effects of di (2-ethylhexyl) phthalate and bisphenol A on thyroid hormone homeostasis in adolescent female rats Xuan Zhang 1 & Yuejiao Zhao 2 & Cheng Cheng 1 & Liuli Li 1 & Mingyang Xiao 1 & Guopei Zhang 1 & Xiaobo Lu 1 Received: 1 April 2020 / Accepted: 29 June 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Phthalates and bisphenols are two typical classes of endocrine-disrupting chemicals (EDCs) which cause endocrine disorder in humans and animals. Phthalates and bisphenols are suggested to be associated with thyroid dysfunction. However, the effects of combined exposure and the detailed mechanisms are yet poorly understood. We investigated the combined effects of di (2ethylhexyl) phthalate (DEHP) and bisphenol A (BPA) on thyroid function during puberty. Female Sprague Dawley rats were gavaged from postnatal 28 to 70 days with a single or combined exposure of DEHP (0, 150, and 750 mg/kg/day) and BPA (0, 20, and 100 mg/kg/day) according to a 3 × 3 factorial design. The thyroid weights reduced after combined exposure to the highest dose of DEHP and BPA, which noted their adverse effects on thyroid. Additionally, DEHP could increase the number of follicular epithelial cells in thyroid. Both DEHP and in combination with BPA could disturb the levels of thyroid hormones in serum, such as TT3 and TT4. Meanwhile, the possible mechanism was also discussed in the present study. DEHP treatment induced a significant increase of phosphorylation of cAMP-response element binding protein (Creb) via estrogen receptor α (Esr1), while the upregulation was nullified by the concomitant presence of BPA. In conclusion, the complex action of DEHP/ BPA mixture may disturb the thyroid hormone homeostasis, which ultimately would affect the development of thyroid during puberty. Keywords Di (2-ethylhexyl) phthalate . Bisphenol A . Combined effects . Thyroid hormone homeostasis . Estrogen receptor α
Introduction Endocrine-disrupting chemicals (EDCs) widely exist in the environment, which have drawn much attention due to their adverse effects on multiple systems. Essentially, these EDCs can disrupt hormone balance by mimicking or blocking hormones (Gore et al. 2015), which would ultimately damage physiology function, such as endocrine and reproductive systems (Riaz et al. 2016) (Ma et al. 2017). Xuan Zhang and Yuejiao Zhao contributed equally to this work. Responsible Editor: Mohamed M. Abdel-Daim * Xiaobo Lu [email protected] 1
Department of Toxicology, School of Public Health, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang 110122, Liaoning Province, People’s Republic of China
2
Cancer Hospital of China Medical University/Liaoning Cancer Hospital & Institute, Shenyang, People’s Republic of China
As typical EDCs, di-2-ethylhexyl phthalate (DEHP) and bisphenol A (BPA) are utilized in a range of consumer products, including personal care products, plastics, and food packaging, leading to widespread human exposure (Guo and Kannan 2012) (Kang et al. 2006) (We
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