Combined effects of BPA and PFOS on fetal cardiac development: in vitro and in vivo experiments
By Ren Zhou, Wei Cheng, Yan Feng, Wei Wang, Fan Liang, Fei Luo, Shoufei Yang, and Yan Wang
Environ. Toxicol. Pharmacol.
June 24, 2020
DOI: 10.1016/j.etap.2020.103434
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.
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