کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6382401 1625953 2014 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Chronic exposure of killifish to a highly polluted environment desensitizes estrogen-responsive reproductive and biomarker genes
ترجمه فارسی عنوان
قرار گرفتن در معرض ازدیاد زیست محیطی به یک محیط بسیار آلوده، ژن های تولید مثل و بیومارکرین پاسخ دهنده استروژن را کاهش می دهد
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم آبزیان
چکیده انگلیسی


- Reproductive biomarker genes in Newark Bay killifish are desensitized to estrogen.
- Gene desensitization indicates pre-transcriptional effects on estrogen signaling.
- Desensitization does not have a metabolic or epigenetic basis (gene methylation).
- Modulation of vitellogenin and choriogenin genes correlates with reproductive impacts.
- Choriogenin L appears less prone to false negatives and may be a sensitive biomarker.

Reproductive and endocrine disruption is commonly reported in aquatic species exposed to complex contaminant mixtures. We previously reported that Atlantic killifish (Fundulus heteroclitus) from the chronically contaminated Newark Bay, NJ, exhibit multiple endocrine disrupting effects, including inhibition of vitellogenesis (yolk protein synthesis) in females and false negative vitellogenin biomarker responses in males. Here, we characterized the effects on estrogen signaling and the transcriptional regulation of estrogen-responsive genes in this model population. First, a dose-response study tested the hypothesis that reproductive biomarkers (vtg1, vtg2, chg H, chg Hm, chg L) in Newark Bay killifish are relatively less sensitive to 17β-estradiol at the transcriptional level, relative to a reference (Tuckerton, NJ) population. The second study assessed expression for various metabolism (cyp1a, cyp3a30, mdr) and estrogen receptor (ER α, ER βa, ER βb) genes under basal and estrogen treatment conditions in both populations. Hepatic metabolism of 17β-estradiol was also evaluated in vitro as an integrated endpoint for adverse effects on metabolism. In the third study, gene methylation was evaluated for promoters of vtg1 (8 CpGs) and vtg2 (10 CpGs) in both populations, and vtg1 promoter sequences were examined for single nucleotide polymorphism (SNPs). Overall, these studies show that multi-chemical exposures at Newark Bay have desensitized all reproductive biomarkers tested to estrogen. For example, at 10 ng/g 17β-estradiol, inhibition of gene induction ranged from 62% to 97% for all genes tested in the Newark Bay population, relative to induction levels in the reference population. The basis for this recalcitrant phenotype could not be explained by a change in 17β-estradiol metabolism, nuclear estrogen receptor expression, promoter methylation (gene silencing) or SNPs, all of which were unaltered and normal in the Newark Bay population. The decreased transcriptional sensitivity of estrogen-responsive genes is suggestive of a broad effect on estrogen receptor pathway signaling, and provides insight into the mechanisms of the endocrine disrupting effects in the Newark Bay population.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Aquatic Toxicology - Volume 152, July 2014, Pages 222-231
نویسندگان
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