摘要：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-γ (IFN-γ), interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α). Results p -NP modulated cytokine secretion by inducing the release of GM-CSF, IFN-γ, IL-1β, IL-4, and IL-10, with a maximum effect at 10−11 M. It reduced the release of TNF-α at 10−13 M, whereas levels of IL-2 and IL-5 remained below the detection limit. IL-6 and IL-8 levels were 100–1,000 times higher than those of other cytokines, and they were not affected by p -NP. We observed significant differences from controls (ethanol alone) only for GM-CSF and IL-10. Conclusion An 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.
关键词：chorionic villous explants; cytokine network; endocrine disruptors; human placenta; para-nonylphenol
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