The Ninth People's Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, PR China; School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China.
School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China.
Environ Toxicol Pharmacol. 2020 Nov;80:103434. doi: 10.1016/j.etap.2020.103434. Epub 2020 Jun 13.
Analyses of the combined effects of different EDCs are both important and difficult. This study attempts to evaluate the individual and combined effects of BPA and PFOS on heart development. Sprague-Dawley rats received individual or combined PFOS and BPA for 19 days during pregnancy. The results show that the combined BPA and PFOS exposure could lead to a morphological change in the fetal rat heart. An increase in the interventricular septal thickness (IVS) of approximately 20 % (391 μm in control vs 464 μm in combined exposure) was observed in the fetal rat hearts after the combined exposure to nearly 2000 μg/L PFOS and 100 μg/L BPA through drinking water. The total collagen and dynamin-related protein 1 (Drp1) mRNA level was increased in the fetal hearts exposed to the combination of 2000 μg/L PFOS and 100 μg/L BPA. However, the cell number in the IVS did not significantly change. Based on the previous literature, we believe that the combined exposure to BPA and PFOS had a synergistic effect on the thickness of the IVS. The combined exposure to 40 μg/L PFOS and 2 μg/L BPA failed to cause significant damage to the embryonic heart. The individual and combined effects and the mechanism of the effects of BPA and PFOS on heart development were further investigated by an in vitro study. Embryonic stem cells were administered individual or combined 10 ng/mL BPA and 100 ng/mL PFOS for 14 days during the cardiac differentiation period. The results show that exposure to the combination of 100 ng/mL PFOS and 10 ng/mL BPA could increase the cardiomyocyte size and collagen content. A selective inhibitor of Drp1, Mdivi-1, could inhibit the cardiomyocyte size enlargement but not the collagen content increase caused by the combined exposure. Thus, we believe that although the combined exposure to PFOS and BPA could affect mitochondrial biogenesis and collagen expression, these two effects seem to be relatively independent. Based on these results, this research concludes that combined exposure to PFOS and BPA could specifically lead to increased collagen and IVS thickening in heart development.
分析不同 EDC 的联合效应既重要又困难。本研究试图评估 BPA 和 PFOS 单独及联合对心脏发育的影响。在妊娠期间，Sprague-Dawley 大鼠通过饮用水接受单独或联合的 PFOS 和 BPA 处理 19 天。结果表明，联合暴露于 BPA 和 PFOS 可导致胎鼠心脏形态发生变化。在联合暴露于近 2000μg/L PFOS 和 100μg/L BPA 后，胎鼠心脏的室间隔厚度（IVS）增加约 20%（对照组为 391μm，联合组为 464μm）。在联合暴露于 2000μg/L PFOS 和 100μg/L BPA 的胎鼠心脏中，总胶原蛋白和动力相关蛋白 1（Drp1）mRNA 水平增加。然而，IVS 中的细胞数量没有显著变化。根据之前的文献，我们认为 BPA 和 PFOS 的联合暴露对 IVS 的厚度有协同作用。联合暴露于 40μg/L PFOS 和 2μg/L BPA 不会对胚胎心脏造成明显损伤。通过体外研究进一步研究了 BPA 和 PFOS 对心脏发育的单独和联合作用及其作用机制。在心脏分化期间，胚胎干细胞单独或联合给予 10ng/mL BPA 和 100ng/mL PFOS 处理 14 天。结果表明，暴露于 100ng/mL PFOS 和 10ng/mL BPA 的联合处理可增加心肌细胞大小和胶原蛋白含量。Drp1 的选择性抑制剂 Mdivi-1 可抑制联合暴露引起的心肌细胞大小增大，但不能抑制胶原蛋白含量的增加。因此，我们认为，尽管联合暴露于 PFOS 和 BPA 可能会影响线粒体生物发生和胶原蛋白表达，但这两种效应似乎相对独立。基于这些结果，本研究得出结论，联合暴露于 PFOS 和 BPA 可能会特异性导致心脏发育中胶原蛋白和 IVS 增厚。
