ToxSci Advance Access published online on March 14, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm051
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Tetrabromodiphenyl Ether (BDE 47) Evokes Estrogenicity and Calbindin-D9k Expression Through an Estrogen Receptor-Mediated Pathway in the Uterus of Immature Rats
1 Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 361-763 Republic of Korea 2 Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, BC, V6H 3V5 Canada
# Correspondence: Dr. Eui-Bae Jeung, Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Research Institute of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 361-763, Republic of Korea; Phone: +82-43-261-2397; Fax: +82-43-267-3150; Email: ebjeung{at}chungbuk.ac.kr
Received January 4, 2007; revision received February 13, 2007; accepted February 22, 2007
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Abstract |
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Polybrominated diphenyl ethers (PBDEs), a class of organic brominated flame retardant, have been increasing in the environment, and in the tissues and milk of animals, including humans. To date, 209 PBDE congeners have been reported. Among these, 2,2',4,4'-tetrabromodiphenyl ether (BDE 47) is the dominant congener found in humans and animals. A number of studies have suggested that BDE 47 possesses the potential to disrupt the endocrine system, as well as reproductive functions. This suggests that BDE 47 may act as a developmental neurotoxin and endocrine disruptor (ED). In this study, we employed immature rats as a developmental model to examine the potential involvement of BDE 47 in the induction of calbindin-D9k (CaBP-9k) which a novel biomarker for screening estrogenic compounds. Beginning on postnatal day 16, BDE 47 was administered to immature rats in a dose- and time-dependent manner for 3 days. The biological effects of BDE 47 on the induction of CaBP-9k mRNA and protein were examined by semi-quantitative RT-PCR and Western blotting, respectively. In addition, the physiological role of the estrogen receptor (ER) in BDE 47-induced CaBP-9k expression was examined in vivo. Treatment with a high dose of BDE 47 (200 mg/kg BW/day) resulted in a significant increase in CaBP-9k mRNA and protein 24 h after injection, whereas a modest increase was observed with low and medium doses (50 and 100 mg/kg BW/day). Additionally, treatment with the high dose of BDE 47 induced a clear uterotrophic response. Co-treatment with ICI 182,780, an ER antagonist, completely reversed the BDE 47-induced increases in uterine wet weight and CaBP-9k mRNA and protein. Taken together, these results demonstrate that BDE 47 exposure results in increases in CaBP-9k mRNA and protein in the uteri of immature rats. The biochemical pathway for BDE 47-induced activity may involve the ER-mediated signaling pathway. These results provide new insight into the estrogenic effects of BDE 47 at a critical developmental stage of female reproductive system.
Key Words: BDE 47; Uterus; Endocrine Disruptors; Estrogenicity.
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