Effect Of PFOS On Decidualization And Glucocorticoid-induced Changes In Human Decidual Stromal Cells Of The First Trimester

Context and Objective:Perfluorooctane sulfonate(PFOS)is a kind of persistent and ubiquitous Environmental Endocrine Disruptors with the ability of disrupting endogenous hormones and hard to be degraded,which is widely used as surfactants,lubricants,adhesives,fire retardants and propellants because of its properties of oil-resistance and water-resistance.A large number of experiments have shown that PFOS has potential influence on reproductive function.Human first trimester decidual stromal cells are not completely decidualized and can be induced further,which is vital for the building and maintaining of pregnancy.11β-HSD1 is a glucocorticoid metabolic enzyme converting inactive cortisone into active cortisol,which is highly expressed in decidualized stromal cells.The objective of the present study was to investigate the effects of PFOS on decidualization and glucocorticoid-induced changes in human first trimester decidual stromal cells.Design:Primary human decidual stromal cells were isolated from the decidua tissue of first trimester.The effects of PFOS on decidualized markers(PRL and IGFBP1)and glucocorticoids regeneration enzyme(11β-HSD1)as well as glucocorticoid-induced changes in human decidual stromal cells were detected by PCR or Western Blot.Moreover whether the influence of PFOS on 11β-HSD1 disrupted the glucocorticoids’ effect on Thl associated immune factors(IL-6 and IL-1β)was also detected.Results:The PRL,IGFBP1 and 11β-HSD1 were increased 48 hours after plating as compared with 24 hours and further increased upon induction at both 24 and 48 hours.PFOS(0,0.0001,0.001,0.01,0.1 and 1 μM)decreased PRL,IGFBP1 and 11β-HSD1 in a concentration-dependent manner.Moreover the reductase activity of 11β-HSD1 was significantly reduced by PFOS(0.1μM)in the cells.PFOS(0.1μM)treatment also inhibited cAMP/MPA-induced increases of PRL,IGFBP1 and 11β-HSD1.Treatment of the cells with cortisol(0.1μM)for 24 hours increased PRL,IGFBP1 and 11β-HSD1 significantly,which was significantly attenuated by PFOS(0.1μM).Treatment of the cells with cortisol(0.1μM)decreased IL-6 and IL-1β mRNA levels in the cells as well as IL-6 and IL-1β abundance in the culture medium.Since PFOS exposure can reduce 11β-HSD1 thereby diminishing the capacity of cortisol regeneration from cortisone in the decidual stromal cells,we studied whether exposure to PFOS can attenuate the effect of cortisone on its anti-inflammatory effects.Cortisone(10 μM)treatment of the cells significantly decreased IL-6 and IL-1β mRNA levels in the cells as well as IL-6 and IL-1β abundance in the culture medium,which were significantly attenuated by PFOS(0.1 μM).Conclusions:In the present study we found that the decidual stromal cells of early pregnancy could undergo further decidualization which was impaired by PFOS exposure.Cortisol produced by 11β-HSD1 with the feed-forward regenerating mechanism might play an important role in decidualization in early pregnancy.Furthermore we demonstrated that exposure to PFOS also disrupted the anti-inflammatory effects of cortisone in the decidua in early pregnancy,which may disrupt the maternal-fetal immune tolerance environment.