PMID- 31228822 OWN - NLM STAT- MEDLINE DCOM- 20190918 LR - 20190918 IS - 1090-2414 (Electronic) IS - 0147-6513 (Linking) VI - 181 DP - 2019 Oct 15 TI - In vitro assessment of effects of persistent organic pollutants on the transactivation of estrogen receptor alpha and beta (ERalpha and ERbeta) from the Baikal seal (Pusa sibirica). PG - 463-471 LID - S0147-6513(19)30671-2 [pii] LID - 10.1016/j.ecoenv.2019.06.033 [doi] AB - To assess the effect of exposure to persistent organic pollutants (POPs) on the estrogen receptor (ER) signaling pathway in Baikal seals (Pusa sibirica), we investigated the molecular characterizations and functions of two Baikal seal ER (bsER) isoforms, bsERalpha and bsERbeta. The bsERalpha and bsERbeta cDNA clones isolated have an open reading frame of 595 and 530 amino acid residues, respectively. The tissue distribution analyses of bsER mRNAs showed that bsERalpha transcripts were primarily found in the ovary and uterus, and bsERbeta in the muscle in wild Baikal seals. The immunofluorescence staining assay showed that 17beta-estradiol (E(2)) treatment promoted the nuclear translocation of in vitro-expressed bsERalpha. Transient transfection of bsERalpha in U2OS cells enhanced the transcription of pS2, an ER target gene of E(2). We then measured bsER-mediated transactivation potencies of POPs in an in vitro reporter gene assay system, in which a bsERalpha or bsERbeta expression vector was transfected into COS-1 cells. For comparison, transactivation potencies of POPs on mouse ERs (mERalpha and mERbeta) were also evaluated in the same manner. Results showed significant dose-dependent responses of bsERs and mERs when treated with p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE). bsERs and mERs showed no response when exposed to polychlorinated biphenyls (PCBs) or 2,3,7,8-tetrachlorodibenzo-p-dioxin. Comparison of the dose-response curves of DDTs across species (bsERs vs. mERs) showed that bsERalpha had a response similar to mERalpha, but bsERbeta was less sensitive than mERbeta. Comparing the lowest observable effective concentrations of p,p'-DDT (2.8 muM) and p,p'-DDE (10 muM) for in vitro bsERalpha-mediated transactivation with their hepatic concentrations in wild Baikal seals indicated that some individuals accumulated these compounds at levels comparable to the effective concentrations, suggesting the potential disruption of the bsERalpha signaling pathway in the wild population by these compounds. Co-transfection experiments with bsER and the aryl hydrocarbon receptor (AHR) suggested that high accumulation of estrogenic compounds exerts a synergistic effect with dioxin-like congeners on ER signaling through AHR activation in the wild seal population. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Yoshinouchi, Yuka AU - Yoshinouchi Y AD - Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama, 790-8577, Japan. FAU - Shimizu, Sachiko AU - Shimizu S AD - Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama, 790-8577, Japan. FAU - Lee, Jin-Seon AU - Lee JS AD - Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama, 790-8577, Japan. FAU - Hirano, Masashi AU - Hirano M AD - Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama, 790-8577, Japan. FAU - Suzuki, Ken-Ichi T AU - Suzuki KT AD - Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima, 739-8526, Japan. FAU - Kim, Eun-Young AU - Kim EY AD - Department of Life and Nanopharmaceutical Science and Department of Biology, Kyung Hee University, Hoegi-Dong, Dongdaemun-Gu, Seoul, 130-701, Republic of Korea. FAU - Iwata, Hisato AU - Iwata H AD - Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama, 790-8577, Japan. Electronic address: iwata.hisato.mz@ehime-u.ac.jp. LA - eng PT - Journal Article DEP - 20190619 PL - Netherlands TA - Ecotoxicol Environ Saf JT - Ecotoxicology and environmental safety JID - 7805381 RN - 0 (Dioxins and Dioxin-like Compounds) RN - 0 (Environmental Pollutants) RN - 0 (Estrogen Receptor alpha) RN - 0 (Estrogen Receptor beta) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Dioxins and Dioxin-like Compounds/metabolism/*toxicity MH - Environmental Pollutants/metabolism/*toxicity MH - Estrogen Receptor alpha/*genetics MH - Estrogen Receptor beta/*genetics MH - Female MH - Mice MH - RNA, Messenger/metabolism MH - Seals, Earless MH - Transcriptional Activation/*drug effects OTO - NOTNLM OT - Aryl hydrocarbon receptor OT - Baikal seal OT - Dichlorodiphenyltrichloroethane (DDT) OT - Estrogen receptor OT - Synergistic effect EDAT- 2019/06/23 06:00 MHDA- 2019/09/19 06:00 CRDT- 2019/06/23 06:00 PHST- 2019/03/11 00:00 [received] PHST- 2019/06/06 00:00 [revised] PHST- 2019/06/11 00:00 [accepted] PHST- 2019/06/23 06:00 [pubmed] PHST- 2019/09/19 06:00 [medline] PHST- 2019/06/23 06:00 [entrez] AID - S0147-6513(19)30671-2 [pii] AID - 10.1016/j.ecoenv.2019.06.033 [doi] PST - ppublish SO - Ecotoxicol Environ Saf. 2019 Oct 15;181:463-471. doi: 10.1016/j.ecoenv.2019.06.033. Epub 2019 Jun 19.