Effects Of Perfluorooctane Sulfonate And Its Substitutes On The Transport Of Glucocorticoids And Nutrients In BeWo Cells And Their Mechanisms

Objective: PFOS and its substitute F-53 B,as persistent organic pollutants,can cause a certain degree of harm to the growth and development of the fetus,but its mechanism has not been clarified.The purpose of this study was to elucidate the effects and mechanisms of exposure to PFOS and its substitutes on placental glucocorticoid regulation and nutrient transport.Methods: Human Choriocarcinoma cell(BeWo)was used as a model,0-100 μM PFOS and F-53 B were treated separately,and the CCK-8 method was used to detect the impact of PFOS and F-53 B exposure on cell viability.ELISA method was used to detect the effect of PFOS and F-53 B on the secretion of glucocorticoid regulatory enzymes.Real time fluorescence quantitative PCR was used to detect the effects of PFOS and F-53 B on the expression levels of glucocorticoid regulatory enzymes and nutrient transporter m RNA.Results: PFOS and F-53 B showed significant inhibitory effects on the proliferation activity of BeWo cells after 24 and 48 hours of exposure,with statistically significant differences(P<0.05).And the toxic effect of PFOS on BeWo cells is greater than that of F-53 B.PFOS significantly increased the secretion of 11β-HSD2 and h CG,with a statistically significant difference(P<0.01),while F-53 B exposure showed a significant decrease,with a statistically significant difference(P< 0.01),indicating a dose-response relationship.Both PFOS and F-53 B treatments inhibited the m RNA expression of HSD11B2 and its promoters Sp1 and CGB7,with statistically significant differences(P <0.05).PFOS can inhibit the m RNA expression of PKA.1 μM PFOS and 50 μM F-53 B significantly upregulated the expression of GR gene,with a statistically significant difference(P <0.05).1-50 μM PFOS and F-53 B can increase gene expression of GLUT3,with 100 μM F-53 B significantly inhibited the gene expression of GLUT3,and the difference was statistically significant(P< 0.05).10-100 μM PFOS can significantly inhibit the gene expression of SNAT1,while F-53 B shows no effect.1 μM PFOS and F-53 B significantly inhibit the gene expression of PCFT,100 μM F-53 B can significantly increase the expression of PCFT gene.Conclusion: PFOS and F-54 B can inhibit the proliferation of BeWo cells in a dosedependent and time-dependent manner,and the toxic effect of PFOS on BeWo cells is stronger than that of F-53 B.PFOS can stimulate BeWo cells to secrete h CG,and can stimulate the secretion of h CG by increasing the level of h CG β-The secretion of HSD2 is increased,and PFOS can mediate h CG pair 11 through c AMP/PKA pathway β-Regulation of HSD2.F-53 B can inhibit h CG and 11β-HSD2 secretion,but the inhibition mechanism has nothing to do with c AMP/PKA pathway.PFOS and F-53 B have stronger influence on GLUT3 than GLUT1,and stronger influence on SNAT1 than SNAT2.PFOS and F-53 B have effects on gene expression of nutrient transporters.