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ToxSci Advance Access published online on January 23, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfj102
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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 November 21, 2005
Accepted January 3, 2006

Reproductive and Developmental Toxicology

Dioxin exerts anti-estrogenic actions in a novel dioxin-responsive telomerase-immortalized epithelial cell line of the porcine oviduct (TERT-OPEC)

Sabine Hombach-Klonisch 1, Paola Pocar 2, Johannes Kauffold 3, and Thomas Klonisch 1 *

1 Department of Human Anatomy and Cell Science, University of Manitoba, Faculty of Medicine, Winnipeg, Canada
2 Institute of Anatomy of Domestic Animals, University of Milano, Italy
3 Large Animal Clinic for Theriogenology and Ambulatory Services, Faculty of Veterinary Medicine, University of Leipzig, Germany

* To whom correspondence should be addressed.
Thomas Klonisch, E-mail: klonisch{at}cc.umanitoba.ca


  Abstract

Oviduct epithelial cells are important for the nourishment and survival of ovulated oocytes and early embryos and respond to the steroid hormones estrogen and progesterone. Endocrine disrupting polyhalogenated aromatic hydrocarbons (PHAH) are environmental toxins which in part act through the ligand-activated transcription factor arylhydrocarbon receptor (AhR; dioxin receptor) and exposure to PHAH has been shown to decrease fertility. To investigate effects of PHAHs on the oviduct epithelium as a potential target tissue of dioxin-type endocrine disruptors, we have established a novel telomerase-immortalized oviduct porcine epithelial cell line (TERT-OPEC). TERT-OPEC exhibited active telomerase and the immunoreactive epithelial marker cytokeratin but lacked the stromal marker vimentine. TERT-OPEC contained functional estrogen receptor (ER)-alpha and AhR as determined by the detection of ER-alpha- and AhR-specific target molecules. Treatment of TERT-OPEC with the AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in a significant increase in the production of the P450 microsomal enzyme CYP1A1. Activated AhR caused a down-regulation of ER nuclear protein fraction and significantly decreased ER-signalling in TERT-OPEC as determined by ERE-luciferase transient transfection assays.

In summary, the TCDD-induced and AhR-mediated anti-estrogenic responses by TERT-OPEC suggest that PHAH affect the predominantly estrogen-dependent differentiation of the oviduct epithelium within the fallopian tube, thus, altering the local endocrine milieu potentially resulting in a largely unexplored cause of impaired embryonic development and female infertility.

Keywords: telomerase; immortalization; porcine; oviduct; dioxin; ER; AhR.
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