Endpoint sensitivity in fish endocrine disruption assays: Regulatory implications

Dang, ZhiChao; Li, Kang; Yin, Haowen; Hakkert, Betty C.; Vermeire, Theo

doi:10.1016/j.toxlet.2011.01.016

Cited by 37 publications

(22 citation statements)

References 40 publications

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“…The most commonly reported effects are those resulting from exposure to estrogenic/antiandrogenic chemicals. Feminization of male fishes as evidenced by testicular oocytes or intersex (Jobling et al, 1998;Kavanagh et al, 2004;Dietrich and Krieger, 2009;Blazer et al, 2012) and production of Vtg (Denslow et al, 1999;Jones et al, 2000;Dang et al, 2011;Vajda et al, 2011) has been observed in numerous fish species. In a few cases, population effects are reported (Kidd et al, 2007;An et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Reproductive health of yellow perch Perca flavescens in selected tributaries of the Chesapeake Bay

Blazer

Pinkney

Jenkins

et al. 2013

Science of The Total Environment

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Iwanowicz, Luke R.; Minkkinen, Steven; Draugelis-Dale, Rassa O.; and Uphoff, James H., "Reproductive health of yellow perch Perca flavescens in selected tributaries of the Chesapeake Bay" (2013 H I G H L I G H T S► Reduced recruitment of yellow perch has occurred in urban tributaries of Chesapeake Bay. ► We compared reproductive health biomarkers in perch from two urban, one developing, two less developed watersheds. ► Lack of final maturation, abnormal yolk and zona pellucida were noted in females. ► Leydig cell proliferation was noted in males. Reduced recruitment of yellow perch has been noted for a number of years in certain urbanized watersheds (South and Severn Rivers) of the Chesapeake Bay. Other rapidly developing watersheds such as Mattawoman Creek are more recently showing evidence of reduced recruitment of anadromous fishes. In this study, we used a battery of biomarkers to better document the reproductive health of adult yellow perch collected during spring spawning in [2007][2008][2009]. Perch were collected in the South and Severn Rivers, Mattawoman Creek and the less developed Choptank and Allen's Fresh watersheds for comparison. Gonadosomatic indices, plasma reproductive hormone concentrations, plasma vitellogenin concentrations and gonad histology were evaluated in mature perch of both sexes. In addition, sperm quantity (cell counts) and quality (total and progressive motility, spermatogenic stage and DNA integrity), were measured in male perch. Many of these biomarkers varied annually and spatially, with some interesting statistical results and trends. Male perch from the Choptank and Allen's Fresh had generally higher sperm counts. In 2008 counts were significantly lower in the perch from the Severn when compared to other sites. The major microscopic gonadal abnormality in males was the proliferation of putative Leydig cells, observed in testes from Severn and less commonly, Mattawoman Creek perch. Observations that could significantly impact egg viability were an apparent lack of final maturation, abnormal yolk and thin, irregular zona pellucida. These were observed primarily in ovaries from Severn, South and less commonly Mattawoman Creek perch. The potential association of these observations with urbanization, impervious surface and chemical contaminants is discussed. a b s t r a c t a r t i c l e i n f oPublished by Elsevier B.V.

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Section: Discussionmentioning

confidence: 99%

Reproductive health of yellow perch Perca flavescens in selected tributaries of the Chesapeake Bay

Blazer

Pinkney

Jenkins

et al. 2013

Science of The Total Environment

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“…Vitellogenin (VTG). VTG is a yolk-precursor protein normally expressed in female oviparous species and is a highly responsive biomarker for estrogen receptor agonists, especially in males who carry the VTG gene but do not ordinarily express it at appreciable levels (Sumpter and Jobling, 1995;Ankley et al, 2001;Arukwe and Goksoyr, 2003;Pawlowski et al, 2004;Dang et al, 2011). The VTG endpoint is relatively specific for detecting alterations in circulating levels of estrogen in fish; however, hepatotoxicity would also be expected to affect this endpoint since VTG in synthesized in the liver (Arukwe and Goksoyr, 2003).…”

Section: Gonadosomatic Index (Gsi)mentioning

confidence: 99%

“…GSI is the weight of the gonad normalized by the whole body weight of the fish. Overall, this endpoint has relatively low sensitivity for detecting potential endocrine activity (Dang et al., ), and changes in GSI can result from changes in either whole body wet weight and/or changes in gonad weight. For female fish, GSI can vary depending on spawning status, with smaller GSI values directly following spawning events (Jensen et al., ).…”

Section: Introductionmentioning

confidence: 99%

“…In our experience, there is generally very little variability in tubercle scores (Table ). Changes in secondary sex characteristics are reportedly less sensitive to endocrine activity in the FSTRA relative to gonad histopathology, fecundity, and VTG endpoints (Dang et al., ). Changes in other secondary sex characteristics, such as vertical banding coloration and fatpad development, are also recorded at test termination, but can be even more subjective and variable over time.…”

Section: Introductionmentioning

confidence: 99%

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Challenges and Approaches to Conducting and Interpreting the Amphibian Metamorphosis Assay and the Fish Short‐Term Reproduction Assay

Coady

Lehman

Currie

et al. 2013

Birth Defects Research Pt B

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The amphibian metamorphosis assay (AMA) and the fish short-term reproduction assay (FSTRA) are screening assays designed to detect potential endocrine activity of a test substance. These assays are included in a battery of assays in Tier 1 of U.S. Environmental Protection Agency's Endocrine Disruptor Screening Program. Based on our laboratory's experience with these two assays, we have noted several challenges in the conduct and interpretation of the AMA and FSTRA, including, but not limited to, diseased/parasitized test organisms, failure to meet some guideline performance criteria, and issues selecting and maintaining test concentrations. Various approaches are described for addressing the challenges associated with both the conduct and interpretation of these assays. Historical control data for both the AMA and FSTRA are presented to further understand background occurrences of histopathological phenomena and variability associated with the measured endpoints in these assays. In the historical control database for the AMA, wet weight on day 7 was the most variable endpoint (coefficient of variation = 26%), while developmental stage on day 21 was least variable (coefficient of variation = 0.47%). In the FSTRA, vitellogenin concentrations were the most variable endpoint (coefficient of variation = 47-84%), while fertility was the least variable endpoint (coefficient of variation = 1.5%) among historical controls.

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“…The appearance of histological sections, coupled with analysis of Vtg expression, is considered one of the most sensitive endpoints for determining whether endocrine disruption has occurred [67]. Exposure to both estrogenic and androgenic compounds has been shown to reduce GSI and increase the incidence of germ cell necrosis, which may represent an interruption of spermatogenesis [40], [68], [69].…”

Section: Discussionmentioning

confidence: 99%

From ‘Omics to Otoliths: Responses of an Estuarine Fish to Endocrine Disrupting Compounds across Biological Scales

Brander

Connon

et al. 2013

PLoS ONE

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Endocrine disrupting chemicals (EDCs) cause physiological abnormalities and population decline in fishes. However, few studies have linked environmental EDC exposures with responses at multiple tiers of the biological hierarchy, including population-level effects. To this end, we undertook a four-tiered investigation in the impacted San Francisco Bay estuary with the Mississippi silverside (Menidia audens), a small pelagic fish. This approach demonstrated links between different EDC sources and fish responses at different levels of biological organization. First we determined that water from a study site primarily impacted by ranch run-off had only estrogenic activity in vitro, while water sampled from a site receiving a combination of urban, limited ranch run-off, and treated wastewater effluent had both estrogenic and androgenic activity. Secondly, at the molecular level we found that fish had higher mRNA levels for estrogen-responsive genes at the site where only estrogenic activity was detected but relatively lower expression levels where both estrogenic and androgenic EDCs were detected. Thirdly, at the organism level, males at the site exposed to both estrogens and androgens had significantly lower mean gonadal somatic indices, significantly higher incidence of severe testicular necrosis and altered somatic growth relative to the site where only estrogens were detected. Finally, at the population level, the sex ratio was significantly skewed towards males at the site with measured androgenic and estrogenic activity. Our results suggest that mixtures of androgenic and estrogenic EDCs have antagonistic and potentially additive effects depending on the biological scale being assessed, and that mixtures containing androgens and estrogens may produce unexpected effects. In summary, evaluating EDC response at multiple tiers is necessary to determine the source of disruption (lowest scale, i.e. cell line) and what the ecological impact will be (largest scale, i.e. sex ratio).

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Endpoint sensitivity in fish endocrine disruption assays: Regulatory implications

Cited by 37 publications

References 40 publications

Reproductive health of yellow perch Perca flavescens in selected tributaries of the Chesapeake Bay

Reproductive health of yellow perch Perca flavescens in selected tributaries of the Chesapeake Bay

Challenges and Approaches to Conducting and Interpreting the Amphibian Metamorphosis Assay and the Fish Short‐Term Reproduction Assay

From ‘Omics to Otoliths: Responses of an Estuarine Fish to Endocrine Disrupting Compounds across Biological Scales

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