7 research outputs found
Re-evaluating the Significance of Estrone as an Environmental Estrogen
Studies
worldwide have demonstrated the occurrence of feminized
male fish at sites impacted by human and animal wastes. A variety
of chemicals could contribute to this phenomenon, but those receiving
the greatest attention in terms of research and monitoring have been
17β-estradiol (β-E2) and 17α-ethinylestradiol, due
both to their prevalence in the environment and strong estrogenic
potency. A third steroid, estrone (E1), also can occur at high concentrations
in surface waters but generally has been of lesser concern due to
its relatively lower affinity for vertebrate estrogen receptors. In
an initial experiment, male fathead minnow (<i>Pimephales promelas</i>) adults were exposed for 4-d to environmentally relevant levels
of waterborne E1, which resulted in plasma β-E2 concentrations
similar to those found in reproductively active females. In a second
exposure we used <sup>13</sup>C-labeled E1, together with liquid chromatography-tandem
mass spectrometry, to demonstrate that elevated β-E2 measured
in the plasma of the male fish was indeed derived from the external
environment, most likely via a conversion catalyzed by one or more
17β-hydroxysteroid dehydrogenases. The results of our studies
suggest that the potential impact of E1 as an environmental estrogen
currently is underestimated
Re-evaluating the Significance of Estrone as an Environmental Estrogen
Studies
worldwide have demonstrated the occurrence of feminized
male fish at sites impacted by human and animal wastes. A variety
of chemicals could contribute to this phenomenon, but those receiving
the greatest attention in terms of research and monitoring have been
17β-estradiol (β-E2) and 17α-ethinylestradiol, due
both to their prevalence in the environment and strong estrogenic
potency. A third steroid, estrone (E1), also can occur at high concentrations
in surface waters but generally has been of lesser concern due to
its relatively lower affinity for vertebrate estrogen receptors. In
an initial experiment, male fathead minnow (<i>Pimephales promelas</i>) adults were exposed for 4-d to environmentally relevant levels
of waterborne E1, which resulted in plasma β-E2 concentrations
similar to those found in reproductively active females. In a second
exposure we used <sup>13</sup>C-labeled E1, together with liquid chromatography-tandem
mass spectrometry, to demonstrate that elevated β-E2 measured
in the plasma of the male fish was indeed derived from the external
environment, most likely via a conversion catalyzed by one or more
17β-hydroxysteroid dehydrogenases. The results of our studies
suggest that the potential impact of E1 as an environmental estrogen
currently is underestimated
Short-Term Study Investigating the Estrogenic Potency of Diethylstilbesterol in the Fathead Minnow (Pimephales promelas)
Diethylstilbestrol (DES) is a synthetic estrogen that
has been
banned for use in humans, but still is employed in livestock and aquaculture
operations in some parts of the world. Detectable concentrations of
DES in effluent and surface waters have been reported to range from
slightly below 1 to greater than 10 ng/L. Little is known, however,
concerning the toxicological potency of DES in fish. In this study,
sexually mature fathead minnows (Pimephales promelas) of both sexes were exposed to 1, 10, or 100 ng of DES/L of water
in a flow-through system. Tissue concentrations of DES and changes
in a number of estrogen-responsive end points were measured in the
fish at the end of a 4 d exposure and after a 4 d depuration/recovery
period in clean water. Accumulation of DES was sex-dependent, with
females exhibiting higher tissue residues than males after the 4 d
exposure. The observed bioconcentration of DES in the fish was about
1 order of magnitude lower than that predicted on the basis of the
octanol–water partition coefficient of the chemical, suggesting
relatively efficient metabolic clearance by the fish. Exposure to
1, 10, or 100 ng of DES/L caused decreased testis weight and morphological
demasculinization of males (regression of dorsal nuptial tubercles).
Diethylstilbesterol induced plasma vitellogenin (VTG) in both sexes
at water concentrations ≥10 ng/L; this response (especially
in males) persisted through the end of the 4 d recovery period. Hepatic
transcripts of VTG and estrogen receptor-α also were affected
at DES concentrations ≥10 ng/L. Evaluation of transcript profiles
in the liver of females using a 15K-gene fathead minnow microarray
revealed a concentration-dependent change in gene expression, with
mostly up-regulated transcripts after the exposure and substantial
numbers of down-regulated gene products after depuration. Genes previously
identified as vitellogenesis-related and regulated by 17β-estradiol
were significantly enriched among those differentially expressed following
exposure to DES. Overall, our studies show that DES causes a range
of responses in fish at water concentrations comparable to those reported
in the environment and that in vivo potency of the estrogen is on
par with that of the better-studied estrogenic contaminant 17α-ethinylestradiol
Ecotoxicogenomics to Support Ecological Risk Assessment: A Case Study with Bisphenol A in Fish
Effects of bisphenol A (BPA) on ovarian transcript profiles as well as targeted end points with endocrine/reproductive relevance were examined in two fish species, fathead minnow (<i>Pimephales promelas</i>) and zebrafish (<i>Danio rerio</i>), exposed in parallel using matched experimental designs. Four days of waterborne exposure to 10 μg BPA/L caused significant vitellogenin induction in both species. However, zebrafish were less sensitive to effects on hepatic gene expression and steroid production than fathead minnow and the magnitude of vitellogenin induction was more modest (i.e., 3-fold compared to 13 000-fold in fathead minnow). The concentration–response at the ovarian transcriptome level was nonmonotonic and violated assumptions that underlie proposed methods for estimating hazard thresholds from transcriptomic results. However, the nonmonotonic profile was consistent among species and there were nominal similarities in the functions associated with the differentially expressed genes, suggesting potential activation of common pathway perturbation motifs in both species. Overall, the results provide an effective case study for considering the potential application of ecotoxicogenomics to ecological risk assessments and provide novel comparative data regarding effects of BPA in fish
Prioritization of Contaminants of Emerging Concern in Wastewater Treatment Plant Discharges Using Chemical:Gene Interactions in Caged Fish
We
examined whether contaminants present in surface waters could
be prioritized for further assessment by linking the presence of specific
chemicals to gene expression changes in exposed fish. Fathead minnows
were deployed in cages for 2, 4, or 8 days at three locations near
two different wastewater treatment plant discharge sites in the Saint
Louis Bay, Duluth, MN and one upstream reference site. The biological
impact of 51 chemicals detected in the surface water of 133 targeted
chemicals was determined using biochemical endpoints, exposure activity
ratios for biological and estrogenic responses, known chemical:gene
interactions from biological pathways and knowledge bases, and analysis
of the covariance of ovary gene expression with surface water chemistry.
Thirty-two chemicals were significantly linked by covariance with
expressed genes. No estrogenic impact on biochemical endpoints was
observed in male or female minnows. However, bisphenol A (BPA) was
identified by chemical:gene covariation as the most impactful estrogenic
chemical across all exposure sites. This was consistent with identification
of estrogenic effects on gene expression, high BPA exposure activity
ratios across all test sites, and historical analysis of the study
area. Gene expression analysis also indicated the presence of nontargeted
chemicals including chemotherapeutics consistent with a local hospital
waste stream. Overall impacts on gene expression appeared to be related
to changes in treatment plant function during rain events. This approach
appears useful in examining the impacts of complex mixtures on fish
and offers a potential route in linking chemical exposure to adverse
outcomes that may reduce population sustainability
Ecotoxicogenomics to Support Ecological Risk Assessment: A Case Study with Bisphenol A in Fish
Effects of bisphenol A (BPA) on ovarian transcript profiles as well as targeted end points with endocrine/reproductive relevance were examined in two fish species, fathead minnow (<i>Pimephales promelas</i>) and zebrafish (<i>Danio rerio</i>), exposed in parallel using matched experimental designs. Four days of waterborne exposure to 10 μg BPA/L caused significant vitellogenin induction in both species. However, zebrafish were less sensitive to effects on hepatic gene expression and steroid production than fathead minnow and the magnitude of vitellogenin induction was more modest (i.e., 3-fold compared to 13 000-fold in fathead minnow). The concentration–response at the ovarian transcriptome level was nonmonotonic and violated assumptions that underlie proposed methods for estimating hazard thresholds from transcriptomic results. However, the nonmonotonic profile was consistent among species and there were nominal similarities in the functions associated with the differentially expressed genes, suggesting potential activation of common pathway perturbation motifs in both species. Overall, the results provide an effective case study for considering the potential application of ecotoxicogenomics to ecological risk assessments and provide novel comparative data regarding effects of BPA in fish
Ecotoxicogenomics to Support Ecological Risk Assessment: A Case Study with Bisphenol A in Fish
Effects of bisphenol A (BPA) on ovarian transcript profiles as well as targeted end points with endocrine/reproductive relevance were examined in two fish species, fathead minnow (<i>Pimephales promelas</i>) and zebrafish (<i>Danio rerio</i>), exposed in parallel using matched experimental designs. Four days of waterborne exposure to 10 μg BPA/L caused significant vitellogenin induction in both species. However, zebrafish were less sensitive to effects on hepatic gene expression and steroid production than fathead minnow and the magnitude of vitellogenin induction was more modest (i.e., 3-fold compared to 13 000-fold in fathead minnow). The concentration–response at the ovarian transcriptome level was nonmonotonic and violated assumptions that underlie proposed methods for estimating hazard thresholds from transcriptomic results. However, the nonmonotonic profile was consistent among species and there were nominal similarities in the functions associated with the differentially expressed genes, suggesting potential activation of common pathway perturbation motifs in both species. Overall, the results provide an effective case study for considering the potential application of ecotoxicogenomics to ecological risk assessments and provide novel comparative data regarding effects of BPA in fish