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)-1beta, 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-1beta, 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 from controls (ethanol alone) only for GM-CSF and IL-10.


CONCLUSIONS
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.
Bechi
Nicoletta
N
Department of Physiology, University of Siena, Siena, Italy.
Ietta
Francesca
F
Romagnoli
Roberta
R
Jantra
Silke
S
Cencini
Marco
M
Galassi
Gianmichele
G
Serchi
Tommaso
T
Corsi
Ilaria
I
Focardi
Silvano
S
Paulesu
Luana
L
D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism*; D004785:Environmental Pollutants / Q000032:analysis* / Q000633:toxicity; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D010636:Phenols / Q000032:analysis* / Q000633:toxicity*; D010920:Placenta / Q000166:cytology / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D004785:Environmental Pollutants; D007378:Interleukins; D010636:Phenols; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; C041594:4-nonylphenol