Wang Zi-Yi, Lu Jing, Zhang Yuan-Zhen, Zhang Ming, Liu Teng, Qu Xin-Lan
Reproductive Medicine Center, Zhongnan Hospital of Wuhan UniversityWuhan 430071, Hubei Province, People's Republic of China; Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan UniversityWuhan 430071, Hubei Province, People's Republic of China.
Int J Clin Exp Pathol. 2015 Nov 1;8(11):14355-64. eCollection 2015.
Bisphenol A (BPA) is a kind of environmental endocrine disruptors (EEDs) that interfere embryo implantation. Trophoblast invasion plays a crucial role during embryo implantation. In this study, the effects of BPA on invasion ability of human trophoblastic cell line BeWo and its possible mechanism were investigated. BeWo cells were exposed to BPA and co-cultured with human endometrial cells to mimic embryo implantation in transwell model. The proliferation and invasion capability of BeWo cells were detected. The expression of E-cadherin, DNMT1, MMP-2, MMP-9, TIMP-1 and TIMP-2 were also analyzed. The results showed that the invasion capability of BeWo was reduced after daily exposure to BPA. BPA had biphasic effect on E-cadherin expression level in BeWo cells and expression level of DNMT1 was decreased when treated with BPA. Moreover, BPA treatment also changed the balance of MMPs/TIMPs in BeWo cells by down-regulating MMP-2, MMP-9 and up-regulating TIMP-1, TIMP-2 with increasing BPA concentration. Taken together, these results showed that BPA treatment could reduce the invasion ability of BeWo cells and alter the expression level of E-cadherin, DNMT1, TIMP-1, TIMP-2, MMP-2, and MMP-9. Our study would help us to understand the possible mechanism of BPA effect on invasion ability of human trophoblastic cell line BeWo.
双酚A(BPA)是一种干扰胚胎着床的环境内分泌干扰物(EEDs)。滋养层细胞侵袭在胚胎着床过程中起关键作用。本研究探讨了BPA对人滋养层细胞系BeWo侵袭能力的影响及其可能机制。将BeWo细胞暴露于BPA,并与人子宫内膜细胞共培养,以在Transwell模型中模拟胚胎着床。检测BeWo细胞的增殖和侵袭能力。还分析了E-钙黏蛋白、DNMT1、MMP-2、MMP-9、TIMP-1和TIMP-2的表达。结果表明,每天暴露于BPA后,BeWo的侵袭能力降低。BPA对BeWo细胞中E-钙黏蛋白的表达水平有双相作用,用BPA处理时DNMT1的表达水平降低。此外,随着BPA浓度的增加,BPA处理还通过下调MMP-2、MMP-9和上调TIMP-1、TIMP-2改变了BeWo细胞中MMPs/TIMPs的平衡。综上所述,这些结果表明,BPA处理可降低BeWo细胞的侵袭能力,并改变E-钙黏蛋白、DNMT1、TIMP-1、TIMP-2、MMP-2和MMP-9的表达水平。我们的研究将有助于我们了解BPA对人滋养层细胞系BeWo侵袭能力影响的可能机制。