Combined effects of di (2-ethylhexyl) phthalate and bisphenol A on thyroid hormone homeostasis in adolescent female rats

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 (2-ethylhexyl) 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 x 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 alpha (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.