Interactions between chemical and climate stressors: A role for mechanistic toxicology in assessing climate change risks

Incorporation of global climate change (GCC) effects into assessments of chemical risk and injury requires integrated examinations of chemical and nonchemical stressors. Environmental variables altered by GCC (temperature, precipitation, salinity, pH) can influence the toxicokinetics of chemical absorption, distribution, metabolism, and excretion as well as toxicodynamic interactions between chemicals and target molecules. In addition, GCC challenges processes critical for coping with the external environment (water balance, thermoregulation, nutrition, and the immune, endocrine, and neurological systems), leaving organisms sensitive to even slight perturbations by chemicals when pushed to the limits of their physiological tolerance range. In simplest terms, GCC can make organisms more sensitive to chemical stressors, while alternatively, exposure to chemicals can make organisms more sensitive to GCC stressors. One challenge is to identify potential interactions between nonchemical and chemical stressors affecting key physiological processes in an organism. We employed adverse outcome pathways, constructs depicting linkages between mechanism-based molecular initiating events and impacts on individuals or populations, to assess how chemical- and climate-specific variables interact to lead to adverse outcomes. Case examples are presented for prospective scenarios, hypothesizing potential chemicalGCC interactions, and retrospective scenarios, proposing mechanisms for demonstrated chemicalclimate interactions in natural populations. Understanding GCC interactions along adverse outcome pathways facilitates extrapolation between species or other levels of organization, development of hypotheses and focal areas for further research, and improved inputs for risk and resource injury assessments. Environ. Toxicol. Chem. 2013;32:3248. (c) 2012 SETA

Differential Gene Expression in Liver, Gill, and Olfactory Rosettes of Coho Salmon (Oncorhynchus kisutch) After Acclimation to Salinity.

Most Pacific salmonids undergo smoltification and transition from freshwater to saltwater, making various adjustments in metabolism, catabolism, osmotic, and ion regulation. The molecular mechanisms underlying this transition are largely unknown. In the present study, we acclimated coho salmon (Oncorhynchus kisutch) to four different salinities and assessed gene expression through microarray analysis of gills, liver, and olfactory rosettes. Gills are involved in osmotic regulation, liver plays a role in energetics, and olfactory rosettes are involved in behavior. Between all salinity treatments, liver had the highest number of differentially expressed genes at 1616, gills had 1074, and olfactory rosettes had 924, using a 1.5-fold cutoff and a false discovery rate of 0.5. Higher responsiveness of liver to metabolic changes after salinity acclimation to provide energy for other osmoregulatory tissues such as the gills may explain the differences in number of differentially expressed genes. Differentially expressed genes were tissue- and salinity-dependent. There were no known genes differentially expressed that were common to all salinity treatments and all tissues. Gene ontology term analysis revealed biological processes, molecular functions, and cellular components that were significantly affected by salinity, a majority of which were tissue-dependent. For liver, oxygen binding and transport terms were highlighted. For gills, muscle, and cytoskeleton-related terms predominated and for olfactory rosettes, immune response-related genes were accentuated. Interaction networks were examined in combination with GO terms and determined similarities between tissues for potential osmosensors, signal transduction cascades, and transcription factors

Impacts of Hypersaline Acclimation on Chlorpyrifos Toxicity to Salmonids

As part of their unique life cycle, most Pacific salmonids transition from freshwater to saltwater, requiring various adjustments in physiology. However, molecular mechanisms underlying this transition are largely unknown. Additionally, acclimation to hypersaline conditions enhances the acute toxicity of certain thioether organophosphate and carbamate pesticides in some species of euryhaline fish, yet sublethal impacts have been far less studied. The current study aimed to determine underlying molecular mechanisms of Pacific salmonid smoltification, as well as determine how hypersaline acclimation impacts acute and sublethal toxicity of a common organophosphate pesticide, chlorpyrifos (CPF). A transcriptomics approach was used to assess differential gene expression in coho salmon (Oncorhynchus kisutch) liver, gills, and olfactory rosettes after salinity acclimation and found that the majority of the altered genes were tissue and salinity concentration dependent. From the few shared genes, a potential osmosenor was identified. Osmotic signal transduction cascades were also impacted in the three tissues. Salinity acclimation was then coupled with CPF to determine impacts on acute toxicity. Time to death of rainbow trout (Oncorhynchus mykiss) by CPF was more rapid in freshwater than in hypersaline water (16 ppth). Salinity acclimation did not impact metabolism, precipitation, or acetylcholinesterase inhibition of CPF. In contrast, mRNA expression of certain neurological targets was upregulated in saltwater acclimated fish, consistent with diminished neuronal signaling which may protect fish from cholinergic overload associated with acetylcholinesterase inhibition. Sublethal experiments, which are more environmentally relevant, were conducted to determine impacts on olfaction. Combined acclimation and exposure to CPF impacted rainbow trout olfaction at the molecular, physiological, and behavioral levels. Concurrent exposure to hypersalinity and 0.5 µg/L CPF upregulated four genes that inhibit olfactory signal transduction. At the physiological level, hypersalinity and chlorpyrifos caused a decrease in sensory response to the amino acid L-serine and the bile salt taurocholic acid. Combined acclimation and exposure also negatively impacted behavior and reduced the avoidance of a predator cue (L-serine). Overall, these results will be very useful in risk assessment strategies evaluating compounds of this nature in estuarine environments and freshwater environments that may be altered by hypersaline stress or rising sea levels

A sermon, Sound Resounds in Zion, Preached at Virtual Chapel Service February 17, 2021

Sermon A Sound Resounds in Zion preached on Joel 2:1-2, 12-17 by Chynaah Maryoung-Cooke Virtual weekly chapel service held via Zoom on February 17, 2021. Digital video recording (mp4). Duration: 15 minutes 37 seconds

Differential Gene Expression in Liver, Gill, and Olfactory Rosettes of Coho Salmon (Oncorhynchus kisutch) After Acclimation to Salinity

Most Pacific salmonids undergo smoltification and transition from freshwater to saltwater, making various adjustments in metabolism, catabolism, osmotic, and ion regulation. The molecular mechanisms underlying this transition are largely unknown. In the present study, we acclimated coho salmon (Oncorhynchus kisutch) to four different salinities and assessed gene expression through microarray analysis of gills, liver, and olfactory rosettes. Gills are involved in osmotic regulation, liver plays a role in energetics, and olfactory rosettes are involved in behavior. Between all salinity treatments, liver had the highest number of differentially expressed genes at 1616, gills had 1074, and olfactory rosettes had 924, using a 1.5-fold cutoff and a false discovery rate of 0.5. Higher responsiveness of liver to metabolic changes after salinity acclimation to provide energy for other osmoregulatory tissues such as the gills may explain the differences in number of differentially expressed genes. Differentially expressed genes were tissue- and salinity-dependent. There were no known genes differentially expressed that were common to all salinity treatments and all tissues. Gene ontology term analysis revealed biological processes, molecular functions, and cellular components that were significantly affected by salinity, a majority of which were tissue-dependent. For liver, oxygen binding and transport terms were highlighted. For gills, muscle, and cytoskeleton-related terms predominated and for olfactory rosettes, immune response-related genes were accentuated. Interaction networks were examined in combination with GO terms and determined similarities between tissues for potential osmosensors, signal transduction cascades, and transcription factors

Differential Gene Expression in Liver, Gill, and Olfactory Rosettes of Coho Salmon (Oncorhynchus kisutch) After Acclimation to Salinity.

Most Pacific salmonids undergo smoltification and transition from freshwater to saltwater, making various adjustments in metabolism, catabolism, osmotic, and ion regulation. The molecular mechanisms underlying this transition are largely unknown. In the present study, we acclimated coho salmon (Oncorhynchus kisutch) to four different salinities and assessed gene expression through microarray analysis of gills, liver, and olfactory rosettes. Gills are involved in osmotic regulation, liver plays a role in energetics, and olfactory rosettes are involved in behavior. Between all salinity treatments, liver had the highest number of differentially expressed genes at 1616, gills had 1074, and olfactory rosettes had 924, using a 1.5-fold cutoff and a false discovery rate of 0.5. Higher responsiveness of liver to metabolic changes after salinity acclimation to provide energy for other osmoregulatory tissues such as the gills may explain the differences in number of differentially expressed genes. Differentially expressed genes were tissue- and salinity-dependent. There were no known genes differentially expressed that were common to all salinity treatments and all tissues. Gene ontology term analysis revealed biological processes, molecular functions, and cellular components that were significantly affected by salinity, a majority of which were tissue-dependent. For liver, oxygen binding and transport terms were highlighted. For gills, muscle, and cytoskeleton-related terms predominated and for olfactory rosettes, immune response-related genes were accentuated. Interaction networks were examined in combination with GO terms and determined similarities between tissues for potential osmosensors, signal transduction cascades, and transcription factors

Reconstitution Studies of Pesticides and Surfactants Exploring the Cause of Estrogenic Activity Observed in Surface Waters of the San Francisco Bay Delta

To evaluate the potential role of endocrine disruption in the decline of pelagic fishes in the San Francisco Bay Delta of California, various surface water samples were collected, extracted, and found to elicit estrogenic activity in laboratory fish. Chemical analysis of the estrogenic samples indicated 2 pesticides (bifenthrin, diuron), 2 alkyphenols (AP), and mixtures of 2 types of alkyphenol polyethoxylates (APEOs). Evaluation of estrogenic activity was further characterized by in vitro bioassays using rainbow trout hepatocytes (<i>Oncorhynchus mykiss</i>) and in vivo studies with Japanese medaka (<i>Oryzias latipes</i>). In the in vitro bioassays, hepatocytes exposed to the pesticides alone or in combination with the AP/APEO mixtures at concentrations observed in surface waters failed to show estrogenic activity (induction of vitelloginin mRNA). In the in vivo bioassays, medaka exposed to individual pesticides or to AP/APEO alone did not have elevated VTG at ambient concentrations. However, when the pesticides were combined with AP/APEOs in the 7-day exposure a significant increase in VTG was observed. Exposure to a 5-fold higher concentration of the AP/APEO mixture alone also significantly induced VTG. In contrast to earlier studies with permethrin, biotransformation of bifenthrin to estrogenic metabolites was not observed in medaka liver microsomes and cytochrome P450 was not induced with AP/APEO treatment. These results showed that mixtures of pesticides with significantly different modes of action and AP/APEOs at environmentally relevant concentrations may be associated with estrogenic activity measured in water extracts and feral fish that have been shown to be in population decline in the San Francisco Bay Delta