Environmental Levels of para-Nonylphenol Are Able to Affect Cytokine Secretion in Human Placenta

BACKGROUND: Para-Nonylphenol (p-NP) is a metabolite of alkylphenols widely used in the chemical industry and manufacturing. It accumulates in the environment, where it acts with estrogen-like activity. We previously showed that p-NP acts on human placenta by inducing trophoblast differentiation and apoptosis. OBJECTIVE: The aim of the present study was to investigate the effect of p-NP on cytokine secretion in human placenta. METHODS: In vitro cultures of chorionic villous explants from human placenta in the first trimester of pregnancy were treated with p-NP (10(-13), 10(-11), and 10(-9) M) in 0.1% ethanol as vehicle. Culture medium was collected after 24 hr and assayed by specific immunoassays for the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-gamma (IFN-gamma), interleukin (IL)-I beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-alpha). RESULTS: p-NP modulated cytokine secretion by inducing the release of GM-CSF, IFN-gamma, IL-1 beta, IL-4, and IL-10, with a maximum effect at 10(-11) M. It reduced the release of TNF-alpha at 10(-13) M, whereas levels of IL-2 and IL-5 remained below the detection limit. IL-6 and IL-8 levels were 1001,000 times higher than those of other cytokines, and they were not affected by p-NP. We observed significant differences front controls (ethanol alone) only for GM-CSF and IL-10. CONCLUSION: All unbalanced cytokine network at the maternal-fetal interface may result in implantation failure, pregnancy loss, or other complications. The effects of extremely low doses of p-NP on the placental release of cytokines raise considerable concerns about maternal exposure to this endocrine disruptor during pregnancy.