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

• Published in: Environmental health perspectives Vol. 118; no. 3; pp. 427 - 431
• Main Authors: Bechi, Nicoletta, letta, Francesca, Romagnoli, Roberta, Jantra, Silke, Cencini, Marco, Galassi, Gianmichele, Serchi, Tommaso, Corsi, Ilaria, Focardi, Silvano, Paulesu, Luana
• Format: Journal Article
• Language: English
• Published: Research Triangle Park, NC National Institute of Environmental Health Sciences 01-03-2010; US Department of Health and Human Services
• Subjects: Apoptosis; Biological and medical sciences; Chemical and industrial products toxicology. Toxic occupational diseases; Children's Health; Cytokines; Cytokines - drug effects; Cytokines - metabolism; Environmental health; Environmental Pollutants - analysis; Environmental Pollutants - toxicity; Estrogens; Ethanol; Female; Humans; Interferon-gamma - metabolism; Interleukins - metabolism; Medical sciences; Natural killer cells; Phenols - analysis; Phenols - toxicity; Physiological aspects; Placenta; Placenta - cytology; Placenta - drug effects; Placenta - embryology; Placenta - metabolism; Pregnancy; Pregnancy Trimester, First; Secretion; T lymphocytes; Time Factors; Toxicology; Trophoblasts; Tumor Necrosis Factor-alpha - metabolism; Various organic compounds; Italy; Human; para-nonylphenol; cytokine network; Secretion; Toxicity; Cytokine; endocrine disruptors; Endocrine disruptor; Pregnancy; chorionic villous explants; Pollutant; Placenta; human placenta; Environment; Public health
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.0900882

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.