Bisphenol AF (BPAF) is a derivative of bisphenol A (BPA) that is widely used in fluorinated polymers, fluorinated rubber, electronic equipment, plastic optical fibers, etc. Studies have shown that BPAF exposure is associated with a number of diseases; however, little is known about the effects of BPAF on cardiomyocytes. We investigated the impact of chronic exposure to BPAF on cardiomyocytes derived from embryonic stem cells (ESCs). The present study showed that chronic exposure to various concentrations of BPAF (0, 8, 200 and 1000 ng/ml) induces cardiomyocyte hypertrophy. The ratios of microfilaments to mitochondrial length and the ratio of microfilaments to cell nuclei and MYH7b levels indicate that BPAF exposure alters the morphology of the cells and mitochondria. Furthermore, BPAF exposure at concentrations from 8 to 1000 ng/ml results in an increase in G protein-coupled estrogen receptor (GPER) expression. Additionally, our results suggest that these effects of BPAF mediate cardiomyocyte hypertrophy apparently due to an increase in the production of reactive nitrogen species (RNS) via an increase in endothelial NO synthase (eNOS). These results imply that ESC-based myocardial differentiation can be an excellent cellular model to study BPAF-induced cardiotoxicity at the cellular and molecular levels.

中文翻译：

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利用胚胎干细胞衍生的心肌细胞通过GPER / CAM / eNOS途径研究双酚AF的心脏毒性。

双酚AF（BPAF）是双酚A（BPA）的衍生物，广泛用于氟化聚合物，氟化橡胶，电子设备，塑料光纤等中。研究表明BPAF暴露与多种疾病相关；然而，关于BPAF对心肌细胞的作用了解甚少。我们调查了长期暴露于BPAF对源自胚胎干细胞（ESC）的心肌细胞的影响。本研究表明，长期暴露于各种浓度的BPAF（0、8、200和1000 ng / ml）会诱发心肌细胞肥大。微丝与线粒体长度的比率以及微丝与细胞核和MYH7b水平的比率表明BPAF暴露会改变细胞和线粒体的形态。此外，浓度为8到1000 ng / ml的BPAF暴露会导致G蛋白偶联雌激素受体（GPER）的表达增加。此外，我们的结果表明，BPAF的这些作用显然是通过内皮一氧化氮合酶（eNOS）的增加而增加了活性氮物质（RNS）的产生，从而介导了心肌肥大。这些结果表明，基于ESC的心肌分化可能是研究BPAF在细胞和分子水平上引起的心脏毒性的优秀细胞模型。