Tributyltin disrupts fin development in Fundulus heteroclitus from both PCB-sensitive and resistant populations: Investigations of potential interactions between AHR and PPARγ.

Tributyltin (TBT) and dioxin-like polychlorinated biphenyls (PCBs) are environmental contaminants that are highly toxic to fish and co-occur in New Bedford Harbor (NBH), an estuarine Superfund site located in Massachusetts, USA. Atlantic killifish (Fundulus heteroclitus) that reside in NBH (and other highly contaminated sites along the east coast of the United States) have developed resistance to activation of the aryl hydrocarbon receptor (AHR) pathway and the toxicity of dioxin-like chemicals, such as 3,3',4,4',5-pentachlorobiphenyl, PCB126. In many biological systems, TBT disregulates adipose and bone development via the PPARγ-RXR pathway; AHR activation also disrupts adipose and bone homeostasis, potentially through molecular crosstalk between AHR and PPARγ. However, little is known about how co-exposure and the interaction of these pathways modulate the toxicological effects of these contaminants. Here, we tested the hypotheses that TBT would induce teratogenesis in killifish via activation of PPARγ and that PCB126 co-exposure would suppress PPARγ pathway activation in PCB-sensitive killifish from a reference site (Scorton Creek, SC, PCB-sensitive) but not in PCB-tolerant NBH killifish. Killifish embryos from both populations exposed to TBT (50 and 100 nM) displayed caudal fin deformities. TBT did not change the expression of pparg or its target genes related to adipogenesis (fabp11a and fabp1b) in either population. However, expression of osx/sp7, an osteoblast marker gene, and col2a1b, a chondroblast marker gene, was significantly suppressed by TBT only in SC killifish. An RXR-specific agonist, but not a PPARγ-specific agonist, induced caudal fin deformities like those observed in TBT-treated embryos. PCB126 did not induce caudal fin deformities and did not exacerbate TBT-induced fin deformities. Further, PCB126 increased expression of pparg in SC embryos and not NBH embryos, but did not change the expression of fabp1b. Taken together, these results suggest that in killifish embryos the PPARγ pathway is regulated in part by AHR, but is minimally active at least in this early life stage. In killifish, RXR activation, rather than PPARγ activation, appears to be the mechanism by which TBT induces caudal fin teratogenicity, which is not modulated by AHR responsiveness.

Assessing pesticide risks to threatened and endangered species using population models: Findings and recommendations from a CropLife America Science Forum.

This brief communication reports on the main findings and recommendations from the 2014 Science Forum organized by CropLife America. The aim of the Forum was to gain a better understanding of the current status of population models and how they could be used in ecological risk assessments for threatened and endangered species potentially exposed to pesticides in the United States. The Forum panelists' recommendations are intended to assist the relevant government agencies with implementation of population modeling in future endangered species risk assessments for pesticides. The Forum included keynote presentations that provided an overview of current practices, highlighted the findings of a recent National Academy of Sciences report and its implications, reviewed the main categories of existing population models and the types of risk expressions that can be produced as model outputs, and provided examples of how population models are currently being used in different legislative contexts. The panel concluded that models developed for listed species assessments should provide quantitative risk estimates, incorporate realistic variability in environmental and demographic factors, integrate complex patterns of exposure and effects, and use baseline conditions that include present factors that have caused the species to be listed (e.g., habitat loss, invasive species) or have resulted in positive management action. Furthermore, the panel advocates for the formation of a multipartite advisory committee to provide best available knowledge and guidance related to model implementation and use, to address such needs as more systematic collection, digitization, and dissemination of data for listed species; consideration of the newest developments in good modeling practice; comprehensive review of existing population models and their applicability for listed species assessments; and development of case studies using a few well-tested models for particular species to demonstrate proof of concept. To advance our common goals, the panel recommends the following as important areas for further research and development: quantitative analysis of the causes of species listings to guide model development; systematic assessment of the relative role of toxicity versus other factors in driving pesticide risk; additional study of how interactions between density dependence and pesticides influence risk; and development of pragmatic approaches to assessing indirect effects of pesticides on listed species.

Comparative transcriptomics implicates mechanisms of evolved pollution tolerance in a killifish population.

Wild populations of the killifish Fundulus heteroclitus resident in heavily contaminated North American Atlantic coast estuaries have recently and independently evolved dramatic, heritable, and adaptive pollution tolerance. We compared physiological and transcriptome responses to embryonic polychlorinated biphenyl (PCB) exposures between one tolerant population and a nearby sensitive population to gain insight into genomic, physiological and biochemical mechanisms of evolved tolerance in killifish, which are currently unknown. The PCB exposure concentrations at which developmental toxicity emerged, the range of developmental abnormalities exhibited, and global as well as specific gene expression patterns were profoundly different between populations. In the sensitive population, PCB exposures produced dramatic, dose-dependent toxic effects, concurrent with the alterations in the expression of many genes. For example, PCB-mediated cardiovascular system failure was associated with the altered expression of cardiomyocyte genes, consistent with sarcomere mis-assembly. In contrast, genome-wide expression was comparatively refractory to PCB induction in the tolerant population. Tolerance was associated with the global blockade of the aryl hydrocarbon receptor (AHR) signalling pathway, the key mediator of PCB toxicity, in contrast to the strong dose-dependent up-regulation of AHR pathway elements observed in the sensitive population. Altered regulation of signalling pathways that cross-talk with AHR was implicated as one candidate mechanism for the adaptive AHR signalling repression and the pollution tolerance that it affords. In addition to revealing mechanisms of PCB toxicity and tolerance, this study demonstrates the value of comparative transcriptomics to explore molecular mechanisms of stress response and evolved adaptive differences among wild populations.

Stored retinoids in populations of the estuarine fish Fundulus heteroclitus indigenous to PCB-contaminated and reference sites.

Concentrations of retinoids, derivatives of vitamin A, were measured in populations of the nonmigratory estuarine fish Fundulus heteroclitus, indigenous to a reference site and a site highly contaminated with polychlorinated biphenyls (PCBs) to address the hypothesis that contaminant exposure causes depletion of stored retinoids in native fish populations. To assess differences related to chemical exposure, as well as season and diet, hepatic retinoid analyses were conducted using fish collected early and late in the natural spawning season and after laboratory holding. Though hepatic retinoid composition was generally similar among groups, hepatic retinoid concentrations differed. Laboratory-held fish had higher hepatic retinyl ester concentrations than field-collected fish. Among field-collected fish, those collected early in the spawning season had higher hepatic retinyl ester concentrations than those collected later in the spawning season. Although there was no evidence of the dramatic retinoid depletions that have been reported in highly exposed populations of other fish species, hepatic retinoid stores were consistently lower in F. heteroclitus indigenous to the highly PCB-contaminated site. These results are consistent with prior findings that fish from this contaminated site are relatively insensitive to some of the toxic effects of PCB exposures, including retinoid depletion.