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Combined effects of BPA and PFOS on fetal cardiac development: In vitro and in vivo experiments.
Environmental Toxicology and Pharmacology ( IF 4.3 ) Pub Date : 2020-06-13 , DOI: 10.1016/j.etap.2020.103434
Ren Zhou 1 , Wei Cheng 2 , Yan Feng 2 , Wei Wang 2 , Fan Liang 2 , Fei Luo 2 , Shoufei Yang 2 , Yan Wang 3
Affiliation  

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.



中文翻译:

BPA和PFOS对胎儿心脏发育的综合影响:体外和体内实验。

对不同EDC的综合影响进行分析既重要又困难。这项研究试图评估BPA和PFOS对心脏发育的个体和联合作用。Sprague-Dawley大鼠在怀孕期间接受了19天的单独或联合PFOS和BPA。结果表明,BPA和PFOS的联合暴露可能导致胎鼠心脏的形态发生变化。联合暴露于近2000μg/ L PFOS和100μg/ L BPA后,在胎鼠心脏中观察到室间隔厚度(IVS)增加约20%(对照组为391μm,联合暴露为464μm)通过喝水。在暴露于2000μg/ L PFOS和100μg/ L BPA组合的胎儿心脏中,总胶原蛋白和与动力蛋白有关的蛋白1(Drp1)mRNA水平升高。然而,IVS中的细胞数没有明显变化。根据以前的文献,我们认为BPA和PFOS的联合暴露对IVS的厚度具有协同作用。两次暴露于40μg/ L PFOS和2μg/ L BPA的组合未能对胚胎心脏造成重大损害。

通过体外研究进一步研究了BPA和PFOS对心脏发育的个体和综合作用以及作用机理。在心脏分化期间,将胚胎干细胞单独或组合使用10 ng / mL BPA和100​​ ng / mL PFOS,共给药14天。结果表明,暴露于100 ng / mL PFOS和10 ng / mL BPA的组合可以增加心肌细胞的大小和胶原蛋白含量。Drp1的选择性抑制剂Mdivi-1可以抑制心肌细胞大小的扩大,但不能抑制由联合暴露引起的胶原蛋白含量的增加。因此,我们认为,虽然同时接触PFOS和BPA可能会影响线粒体的生物发生和胶原蛋白的表达,但这两种作用似乎是相对独立的。根据这些结果,

更新日期:2020-06-13
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