Chronic exposure of killifish to a highly polluted environment desensitizes estrogen-responsive reproductive and biomarker genes.

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