PFOS Inhibited Normal Functional Development of Placenta Cells via PPARγ Signaling

Abstract

Perfluorooctane sulfonic acid (PFOS), a persistent environmental pollutant, has adverse effects on gestation pregnancy. Peroxisome proliferator-activated receptor γ (<i>PPARγ</i>) is involved in angiogenesis, metabolic processes, anti-inflammatory, and reproductive development. However, the function of <i>PPARγ</i> in PFOS evoked disadvantageous effects on the placenta remain uncertain. Here, we explored the role of <i>PPARγ</i> in PFOS-induced placental toxicity. Cell viability, cell migration, angiogenesis, and mRNA expression were monitored by CCK-8 assay, wound healing assay, tube formation assay, and real-time PCR, respectively. Activation and overexpression of <i>PPARγ</i> were conducted by rosiglitazone or pcDNA-<i>PPARγ</i>, and inhibition and knockdown of <i>PPARγ</i> were performed by GW9662 or <i>si-PPARγ</i>. Results revealed that PFOS decreased cell growth, migration, angiogenesis, and increased inflammation in human HTR-8/SVneo and JEG-3 cells. Placenta diameter and fetal weight decreased in mice treated with PFOS (12.5 mg/kg). In addition, rosiglitazone or pcDNA-<i>PPARγ</i> rescued cell proliferation, migration, angiogenesis, and decreased inflammation induced by PFOS in HTR8/SVneo and JEG-3 cells. Furthermore, GW9662 or <i>si-</i><i>PPARγ</i> exacerbated the inhibition of cell viability, migration, angiogenesis, and aggravated inflammation induced by PFOS in HTR-8/SVneo and JEG-3 cells. Meanwhile, the results of mRNA expression level were consistent with the cell representation. In conclusion, our findings revealed that PFOS induced placenta cell toxicity and functional damage through <i>PPARγ</i> pathway.