Abstract
Perfluorooctane sulfonic acid (PFOS), a persistent environmental pollutant, has adverse effects on gestation pregnancy. Peroxisome proliferator-activated receptor γ (PPARγ) is involved in angiogenesis, metabolic processes, anti-inflammatory, and reproductive development. However, the function of PPARγ in PFOS evoked disadvantageous effects on the placenta remain uncertain. Here, we explored the role of PPARγ 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 PPARγ were conducted by rosiglitazone or pcDNA-PPARγ, and inhibition and knockdown of PPARγ were performed by GW9662 or si-PPARγ. 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-PPARγ rescued cell proliferation, migration, angiogenesis, and decreased inflammation induced by PFOS in HTR8/SVneo and JEG-3 cells. Furthermore, GW9662 or si-PPARγ 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 PPARγ pathway.
Highlights
When HTR-8/SVneo and JEG-3 cells were exposed to Perfluorooctane sulphonate (PFOS) and co-treated with rosiglitazone for 24 h, they were significantly increased, whereas with co-treatment of GW9662 and PFOS they were significantly decreased (Figure 5C,D)
MMP-2 and MMP-9 mRNA expression levels were significantly lifted when cells were treated with PFOS and overexpressed with Peroxisome proliferator-activated receptor γ (PPARγ) (Figure 5E,F), and significantly lowered with PFOS and transfected with si-PPARγ (Figure treated with PFOS and overexpressed with PPARγ (Figure 5E,F), and significantly lowered with PFOS and transfected with si-PPARγ (Figure 5G,H)
We demonstrated whether is in the toxicity of by regulating placental cell growth, angiogenesis, and inflaminvolved in the toxicity of PFOS by regulating placental cell growth, angiogenesis, and matory responses in HTR-8/SVneo and and JEG-3 cells
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Biomedicines 2021, 9, 677 through the placental barrier and induce developmental toxicity, such as in prenatal mortality and fetal growth retardation [6,7]. PPARs are ligand-inducible transcription factors that play crucial roles in angiogenesis, metabolic, anti-inflammatory, reproductive developmental processes, and regulate the expression level of plural genes such as VEGFA and TNF-α [11,12,13]. In terms of the PPAR subtypes, PPARγ is primarily involved in placental development. It is a critical component of trophoblastic differentiation and essential for trophoblastic maturation to establish maternal fetal transport [14,15]. We proposed to elucidate whether PPARγ plays a role in placental toxicity induced by PFOS and whether its mechanism is responsible for disrupting placental function
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