Dioxin exerts anti-estrogenic actions in a novel dioxin-responsive telomerase-immortalized epithelial cell line of the porcine oviduct (TERT-OPEC).
Oviduct epithelial cells are important for the nourishment and survival of ovulated oocytes and early embryos, and they respond to the steroid hormones estrogen and progesterone. Endocrine-disrupting polyhalogenated aromatic hydrocarbons (PHAH) are environmental toxins that act in part 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 vimentin. 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 cytochrome P-450 microsomal enzyme CYP1A1. Activated AhR caused a downregulation of ER nuclear protein fraction and significantly decreased ER-signaling 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. This action then alters the local endocrine milieu, potentially resulting in a largely unexplored cause of impaired embryonic development and female infertility.
Hombach-Klonisch
Sabine
S
Department of Human Anatomy and Cell Science, University of Manitoba, Faculty of Medicine, Winnipeg, Manitoba, Canada.
Pocar
Paola
P
Kauffold
Johannes
J
Klonisch
Thomas
T
D000818:Animals; D002460:Cell Line; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D020847:Estrogen Receptor Modulators / Q000633:toxicity; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter / Q000235:genetics; D008156:Luciferases / Q000378:metabolism; D010057:Oviducts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D013552:Swine; D019098:Telomerase / Q000378:metabolism; D014162:Transfection
D004785:Environmental Pollutants; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D008156:Luciferases; D019363:Cytochrome P-450 CYP1A1; D019098:Telomerase