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ToxSci Advance Access published online on June 21, 2006
Toxicological Sciences, 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
Received April 20, 2006
Accepted June 19, 2006

Endocrine Toxicology

Estrogen-like Response to p-nonylphenol in Human First Trimester Placenta and BeWo Choriocarcinoma Cells

Nicoletta Bechi 1, Francesca Ietta 1, Roberta Romagnoli 1, Silvano Focardi 2, Ilaria Corsi 2, Carlo Buffi 3, and Luana Paulesu 1 *

1 Department of Physiology, University of Siena, via A. Moro, Siena 53100, Italy
2 Department of Environmental Sciences, University of Siena, via A. Mattioli, Siena 53100, Italy
3 Obstetrics and Gynecology Division, USL 7, Hospital, Campostaggia, Siena 53036, Italy

* To whom correspondence should be addressed.
Luana Paulesu, E-mail: paulesu{at}unisi.it


  Abstract

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 is 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 17{beta}-estradiol (17{beta}-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{beta} isoform of 55 kDa. Immunohistochemistry revealed expression of ER{alpha} in the villous cytotrophoblast, whereas ER{beta} was mainly expressed by the syncytiotrophoblast. Treatment of explant cultures with p-NP (10-9 M) and 17{beta}-E2 (10-9 M) significantly increased {beta}-hCG secretion and cell apoptosis but did not modify ERs expression. After 72 hours of exposure, hormone release was significantly higher in p-NP- than 17{beta}-E2-treated explant cultures. By this time, cleavage of caspase-3 was evident in cultures treated with 17{beta}-E2 and p-NP. In BeWo cells, a caspase-3 band of 20-16 kDa was evident after 1 hour of treatment with p-NP and after 24 hours of treatment with 17{beta}-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.

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

The authors certify that all research involving human subjects was done under full compliance with all government policies and the Helsinki Declaration.


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