Aim: 

para-nonylphenol (p-NP) is a metabolite of alkylphenols widely used in chemicals and manufacturer industries. Previous studies have shown that p-NP plays an estrogen-like activity inducing trophoblast differentiation and apoptosis on first trimester human placental tissues. Since cytokines are important mediators of blastocyst implantation and placenta development, we analyzed the effect of p-NP on the release of MIF in in vitro cultures of chorionic villous explants from first trimester human 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 collected after 24 hours and assayed by Luminex using specific BioSurce's Multiplex Bead Immunoassay for the following 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 modulates cytokines secretion by inducing the release of GM-CSF, IL-6, IFN-g, IL-4, IL-8 and IL-1b at 10^-9 M concentration while reducing release of MIF at all three concentrations. Level of IL-2, IL-5, IL-10 and TNF-a was remained under the detection limit both in treated and untreated control cultures.

Conclusion: 

An unbalanced cytokine network may result in implantation failure, pregnancy loss and/or other complications. Our findings on the effects of p-NP on cytokine release raised considerable concern about the implications of maternal exposure to endocrine disruptors during pregnancy.