Effect of para-nonylphenol on cytokine secretion in first trimester human placenta

Objectives:Endocrine disrupter chemicals (EDCs) (e.g. herbicides, fungicides, insecti-cides, industrial chemicals) are environmental pollutants of agricultural or industrial or-igin which may influence human reproductive health. We recently found that para-nonylphenol (p-NP), a metabolite of alkylphenols widely used in chemicals and manufac-turer industries, induces trophoblast differentiation and apoptosis on first trimester humanplacental tissues. We hypothesized that para-nonylphenol may also influence on the cy-tokine production. The aim of the present study is to analyze the effects of p-NP on cy-tokines production by in vitro cultures of chorionic villous explants from first trimesterhuman placenta.Methods:Chorionic villous explants were cultured and treated with p-NP (10-13, 10-11,10-9 M) or only with vehicle (ethanol 0.1%) as control. Culture supernatants were col-lected after 24 hours and assayed by specific BioSurce’s Multiplex Bead Immunoassayfor the cytokines GM-CSF, IL-2, IL-6, TNF-a, IFN-g, IL-4, IL-8, IL-1b, IL-5 and IL-10. The cytokine MIF was assayed by a colorimetric sandwich assay (ELISA).Results:p-NP modulated cytokines secretion by inducing the release of GM-CSF, IL-6,IFN-g, IL-4, IL-8 and IL-1bat 10-9 M concentration while reducing release of MIF at allthree concentrations. Level of IL-2, IL-5, IL10 and TNF? was remained under the detec-tion limit both in treated and untreated control cultures.Conclusion:During the peri-implantation period, a multidirectional cytokine network isnecessary for blastocyst implantation and embryonic development. An unbalanced cyto-kine network may result in implantation failure, pregnancy loss and/or other complica-tions. Our findings on the effects of p-NP on cytokine release raised considerableconcern about the implications of maternal exposure to this chemical duringpregnancy.