Dual effects of bisphenol A on wound healing, involvement of estrogen receptor β

• Published in: Ecotoxicology and environmental safety Vol. 231; p. 113207
• Main Authors: Wen, Xue, Zhu, Man, Li, Zehua, Li, Tao, Xu, Xuewen
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.02.2022; Elsevier
• Subjects: Animals; Benzhydryl Compounds - toxicity; Bisphenol A; Diabetes Mellitus, Experimental; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogen receptor β; Fibroblasts; Mice; Mice, Inbred C57BL; Phenols; Wound Healing; Estrogen receptor β; Fibroblasts; Bisphenol A; Wound healing
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2022.113207

Bisphenol A (BPA) is a ubiquitous environmental pollutant that can specifically induce estrogen receptor β (ERβ) expression, and the latter plays a crucial role during wound healing. However, no study has investigated the association between BPA exposure and skin regeneration. This study aimed to explore the impacts of BPA on wound repair using mice models. C57BL/6 mice were administrated with BPA in two different ways during the process of wound healing—dietary intake (5 and 50 mg/kg) and wound application (1 and 100 nM). Mice primary fibroblasts were exposed to BPA to verify the role of BPA on the function of fibroblasts. We also applied BPA in diabetic mice to evaluate its therapy value. BPA showed dual effects on wound healing, which were dependent on the application routes. Dietary intake of BPA delayed wound healing by suppressing ovarian estrogen secretion, whereas wound application of BPA accelerated skin regeneration via up-regulating wound localized ERβ expression. Highly expressed ERβ enhanced the function of fibroblasts and promoted the transformation from fibroblasts to myofibroblasts. Impacts of BPA on wound healing were dismissed when ERβ was blocked. Moreover, wound application of BPA significantly accelerated wound repair in diabetic mice, but has no significant adverse effect on ovarian hormones levels. The current study indicates that although BPA disrupts the function of the endocrine system when administrated by diet, local application of BPA on wounds shows a superior role in promoting wound repair, and this may provide a novel approach for the therapy of pathologic wound healing. [Display omitted] All the data were presented in the main manuscript and additional supporting files. •BPA showed dual effects on wound healing.•Dietary intake of BPA delayed wound healing by suppressing estrogen secretion.•Wound application of BPA accelerated healing by inducing wound ERβ expression.•Wound application of BPA promoted healing of diabetic wounds.•Wound application of BPA had no obvious impacts on ovarian hormones secretion.