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ToxSci Advance Access originally published online on June 21, 2006
Toxicological Sciences 2006 93(1):75-81; doi:10.1093/toxsci/kfl043
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Estrogen-Like Response to p-Nonylphenol in Human First Trimester Placenta and BeWo Choriocarcinoma Cells

Nicoletta Bechi*, Francesca Ietta*, Roberta Romagnoli*, Silvano Focardi{dagger}, Ilaria Corsi{dagger}, Carlo Buffi{ddagger} and Luana Paulesu*,1

* Department of Physiology, University of Siena, via Aldo Moro, Siena 53100, Italy; {dagger} Department of Environmental Sciences, University of Siena, via A. Mattioli, Siena 53100, Italy; and {ddagger} Obstetrics and Gynecology Division, USL 7, Hospital, Campostaggia, Siena 53036, Italy

Received April 20, 2006; accepted June 19, 2006

p-Nonylphenol (p-NP) is a metabolite of alkylphenol ethoxylates used as surfactants in the manufacturing industry. Although it is reported to have estrogenic activity and to be transferred from the mother to the embryo, no data are available on its effects on the development of the human placenta. In the present study, we investigated estrogen receptors' (ERs) expression in the first trimester human placenta. Using an in vitro model of chorionic villous explants, we then compared the effects of p-NP and 17ß-estradiol (17ß-E2). Finally, a trophoblast-derived choriocarcinoma cell line, BeWo, was used as a model of trophoblast cell differentiation. Our results showed that the first trimester placenta expresses three ER-{alpha} isoforms of 67, 46, and 39 kDa and one ER-ß isoform of 55 kDa. Immunohistochemistry revealed the expression of ER-{alpha} in the villous cytotrophoblast, whereas ER-ß was mainly expressed by the syncytiotrophoblast. Treatment of explant cultures with p-NP (10–9M) and 17ß-E2 (10–9M) significantly increased ß-hCG secretion and cell apoptosis but did not modify ER expression. After 72 h of exposure, hormone release was significantly higher in p-NP– than 17ß-E2–treated explant cultures. By this time, cleavage of caspase-3 was evident in cultures treated with 17ß-E2 and p-NP. In BeWo cells, a caspase-3 band of 20–16 kDa was evident after 1 h of treatment with p-NP and after 24 h of treatment with 17ß-E2 or forskolin. These findings suggest that the human trophoblast may be highly responsive to p-NP and raise concern about maternal exposure in early gestation.

Key Words: p-nonylphenol; endocrine disruptors; estrogen receptors; human placenta; human chorionic gonadotropin; trophoblast apoptosis.


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