Search for: All records

Decades of research into stress responses have highlighted large variation among individuals, populations, and species, and the sources of this variation have been a center of research across disciplines. The most common measure of the vertebrate stress response is glucocorticoids. However, the predictive power of glucocorticoid responses to fitness is surprisingly low. This is partly because the hormone levels rapidly change in response to stressor exposure and elevated levels at one time point can indicate either that glucocorticoids are helping the organism cope with the stressor or that dysregulation of hormone release is harming the organism. Meaning, the fitness consequences of the stressor depends on how efficient the stress responses are at negating the harmful impacts of stressors to cells and tissues. To encompass the idea of the efficiency of stress responses and to integrate cellular and organismal stress responses, a new theoretical model called the Damage-Fitness Model was developed. The model focuses on the downstream effects of stress responses and predicts that the accumulation of damage in cells and tissues (e.g., persistent damage to proteins, lipids, and DNA) negatively impacts fitness components. In this mini-review, we examine evidence supporting the Damage-Fitness Model and explore new directions forward.

 

Although most organisms respond to environmental and social stressors by initiating a stress response that is expected to increase fitness, we currently lack information about how the stress response is integrated across levels of biological organization. Organismal biologists and physiological ecologists have tended to focus on questions related to how the glucocorticoid stress response varies across ecological contexts and is related to fitness, whereas, molecular and cellular biologists have typically investigated the fundamental underlying mechanisms. However, it is becoming increasingly clear that a comprehensive understanding of the evolution of the stress response will require integrative studies that span levels of analyses. This information will be critical for predicting how selection will influence the expression of this complex phenotype at the organismal level, as well as how the integration of the underlying mechanisms will influence the evolutionary response to selection. As diverse organisms are expected to experience rising stress exposure in the face of anthropogenic disturbance and climate change, this information is becoming increasingly urgent. The overarching goals of this symposium were to bring together researchers that study the stress response across levels of organization in diverse organisms to identify important gaps in knowledge and novel research approaches that could be used to advance the field.

 

The eastern oyster, Crassostrea virginica, forms reefs that provide critical services to the surrounding ecosystem. These reefs are at risk from climate change, in part because altered rainfall patterns may amplify local fluctuations in salinity, impacting oyster recruitment, survival, and growth. As in other marine organisms, warming water temperatures might interact with these changes in salinity to synergistically influence oyster physiology. In this study, we used comparative transcriptomics, measurements of physiology, and a field assessment to investigate what phenotypic changes C. virginica uses to cope with combined temperature and salinity stress in the Gulf of Mexico. Oysters from a historically low salinity site (Sister Lake, LA) were exposed to fully crossed temperature (20°C and 30°C) and salinity (25, 15, and 7 PSU) treatments. Using comparative transcriptomics on oyster gill tissue, we identified a greater number of genes that were differentially expressed (DE) in response to low salinity at warmer temperatures. Functional enrichment analysis showed low overlap between genes DE in response to thermal stress compared with hypoosmotic stress and identified enrichment for gene ontologies associated with cell adhesion, transmembrane transport, and microtubule-based process. Experiments also showed that oysters changed their physiology at elevated temperatures and lowered salinity, with significantly increased respiration rates between 20°C and 30°C. However, despite the higher energetic demands, oysters did not increase their feeding rate. To investigate transcriptional differences between populations in situ, we collected gill tissue from three locations and two time points across the Louisiana Gulf coast and used quantitative PCR to measure the expression levels of seven target genes. We found an upregulation of genes that function in osmolyte transport, oxidative stress mediation, apoptosis, and protein synthesis at our low salinity site and sampling time point. In summary, oysters altered their phenotype more in response to low salinity at higher temperatures as evidenced by a higher number of DE genes during laboratory exposure, increased respiration (higher energetic demands), and in situ differential expression by season and location. These synergistic effects of hypoosmotic stress and increased temperature suggest that climate change will exacerbate the negative effects of low salinity exposure on eastern oysters.

 

Vertebrates respond to a diversity of stressors by rapidly elevating glucocorticoid (GC) levels. The changes in physiology and behavior triggered by this response can be crucial for surviving a variety of challenges. Yet the same process that is invaluable in coping with immediate threats can also impose substantial damage over time. In addition to the pathological effects of long-term exposure to stress hormones, even relatively brief elevations can impair the expression of a variety of behaviors and physiological processes central to fitness, including sexual behavior, parental behavior, and immune function. Therefore, the ability to rapidly and effectively terminate the short-term response to stress may be fundamental to surviving and reproducing in dynamic environments. Here we review the evidence that variation in the ability to terminate the stress response through negative feedback is an important component of stress coping capacity. We suggest that coping capacity may also be influenced by variation in the dynamic regulation of GCs—specifically, the ability to rapidly turn on and off the stress response. Most tests of the fitness effects of these traits to date have focused on organisms experiencing severe or prolonged stressors. Here we use data collected from a long-term study of tree swallows (Tachycineta bicolor) to test whether variation in negative feedback, or other measures of GC regulation, predict components of fitness in non-chronically stressed populations. We find relatively consistent, but generally weak relationships between different fitness components and the strength of negative feedback. Reproductive success was highest in individuals that both mounted a robust stress response and had strong negative feedback. We did not see consistent evidence of a relationship between negative feedback and adult or nestling survival: negative feedback was retained in the best supported models of nestling and adult survival, but in two of three survival-related analyses the intercept-only model received only slightly less support. Both negative feedback and stress-induced GC levels—but not baseline GCs—were individually repeatable. These measures of GC activity did not consistently covary across ages and life history stages, indicating that they are independently regulated. Overall, the patterns seen here are consistent with the predictions that negative feedback—and the dynamic regulation of GCs—are important components of stress coping capacity, but that the fitness benefits of having strong negative feedback during the reproductive period are likely to manifest primarily in individuals exposed to chronic or repeated stressors.

 

Abstract Ten years ago, two reviews clarified the need to tie glucocorticoid (GC) levels directly to survival and reproductive measures. Three primary hypotheses emerged from that work: the CORT-Fitness hypothesis, the CORT-Adaptation hypothesis, and the CORT-Tradeoff hypothesis. The two reviews have since been cited nearly 900 times, but no clear consensus has emerged supporting one hypothesis over another. We propose that resource availability may be a major confound across studies. Life-history investment is determined by both allocation and acquisition, but current literature testing among the three GC-fitness hypotheses rarely incorporate metrics of resource availability. In 1986, van Noordwijk and de Jong (vN and dJ) proposed the acquisition/allocation Y-model to explain positive versus negative correlations between reproduction and survival across individuals. Their model elevated resources as critical to evaluating individual allocation strategies (favoring reproduction vs. survival), and therefore provides the ideal framework for testing across the three CORT hypotheses. Here, we review the three hypotheses in light of the last 10 years of data, introduce the vN and dJ framework as a model for fitness/GC hypothesis testing, and discuss best practices for using this framework. We believe incorporation of resource availability will reduce unexplained variability in GC-fitness tests, clarify support among the three hypotheses, and allow for greater power in testing across other context dependencies (e.g., life-history strategy) that likely regulate differential allocation to reproduction versus survival as GCs increase. 

Abstract Negative feedback of the vertebrate stress response via the hypothalamic–pituitary–adrenal (HPA) axis is regulated by glucocorticoid receptors in the brain. Epigenetic modification of the glucocorticoid receptor gene (Nr3c1), including DNA methylation of the promoter region, can influence expression of these receptors, impacting behavior, physiology, and fitness. However, we still know little about the long-term effects of these modifications on fitness. To better understand these fitness effects, we must first develop a non-lethal method to assess DNA methylation in the brain that allows for multiple measurements throughout an organism’s lifetime. In this study, we aimed to determine if blood is a viable biomarker for Nr3c1 DNA methylation in two brain regions (hippocampus and hypothalamus) in adult European starlings (Sturnus vulgaris). We found that DNA methylation of CpG sites in the complete Nr3c1 putative promoter varied among tissue types and was lowest in blood. Although we identified a similar cluster of correlated Nr3c1 putative promoter CpG sites within each tissue, this cluster did not show any correlation in DNA methylation among tissues. Additional studies should consider the role of the developmental environment in producing epigenetic modifications in different tissues. 

Abstract The response of ectotherms to temperature stress is complex, non-linear, and is influenced by life stage and previous thermal exposure. Mortality is higher under constant low temperatures than under a fluctuating thermal regime (FTR) that maintains the same low temperature but adds a brief, daily pulse of increased temperature. Long term exposure to FTR has been shown to increase transcription of genes involved in oxidative stress, immune function, and metabolic pathways, which may aid in recovery from chill injury and oxidative damage. Previous research suggests the transcriptional response that protects against sub-lethal damage occurs rapidly under exposure to fluctuating temperatures. However, existing studies have only examined gene expression after a week or over many months. Here we characterize gene expression during a single temperature cycle under FTR. Development of pupating alfalfa leafcutting bees (Megachile rotundata) was interrupted at the red-eye stage and were transferred to 6°C with a 1-h pulse to 20°C and returned to 6°C. RNA was collected before, during, and after the temperature pulse and compared to pupae maintained at a static 6°C. The warm pulse is sufficient to cause expression of transcripts that repair cell membrane damage, modify membrane composition, produce antifreeze proteins, restore ion homeostasis, and respond to oxidative stress. This pattern of expression indicates that even brief exposure to warm temperatures has significant protective effects on insects exposed to stressful cold temperatures that persist beyond the warm pulse. Megachile rotundata’s sensitivity to temperature fluctuations indicates that short exposures to temperature changes affect development and physiology. Genes associated with developmental patterning are expressed after the warm pulse, suggesting that 1 h at 20°C was enough to resume development in the pupae. The greatest difference in gene expression occurred between pupae collected after the warm pulse and at constant low temperatures. Although both were collected at the same time and temperature, the transcriptional response to one FTR cycle included multiple transcripts previously identified under long-term FTR exposure associated with recovery from chill injury, indicating that the effects of FTR occur rapidly and are persistent. 

Abstract It is frequently hypothesized that animals employ a generalized “stress response,” largely mediated by glucocorticoid (GC) hormones, such as corticosterone, to combat challenging environmental conditions. Under this hypothesis, diverse stressors are predicted to have concordant effects across biological levels of an organism. We tested the generalized stress response hypothesis in two complementary experiments with juvenile and adult male Eastern fence lizards (Sceloporus undulatus). In both experiments, animals were exposed to diverse, ecologically-relevant, acute stressors (high temperature or red imported fire ants, Solenopsis invicta) and we examined their responses at three biological levels: behavioral; physiological (endocrine [plasma corticosterone and blood glucose concentrations] and innate immunity [complement and natural antibodies]); and cellular responses (gene expression of a panel of five heat-shock proteins in blood and liver) at 30 or 90 min post stress initiation. In both experiments, we observed large differences in the cellular response to the two stressors, which contrasts the similar behavioral and endocrine responses. In the adult experiment for which we had innate immune data, the stressors affected immune function independently, and they were correlated with CORT in opposing directions. Taken together, these results challenge the concept of a generalized stress response. Rather, the stress response was context specific, especially at the cellular level. Such context-specificity might explain why attempts to link GC hormones with life history and fitness have proved difficult. Our results emphasize the need for indicators at multiple biological levels and whole-organism examinations of stress. 

Abstract The vertebrate stress response is considered to be a highly conserved suite of responses that are evolved to help animals survive noxious environmental stimuli. The two major pathways of the stress response include the catecholamine release that is part of the autonomic nervous system and comprises the immediate fight-or-flight response, and the slower release of corticosteroids from the hypothalamic–pituitary–adrenal axis that help orchestrate longer-term responses. These two pathways are present in every vertebrate yet examined, and the anatomical and physiological architecture underlying these pathways are consistent. Despite these structural similarities, however, recent data indicate substantial temporal and species variation in the actual regulation of these pathways. For example, activation of both pathways varies seasonally in some species but not others, and responses of both pathways can be extensively modulated by an individual’s previous experience. Consequently, even though the anatomy of the stress response is highly conserved, the activation and functional output is not highly conserved. Given this variation, it is perhaps not surprising that it is proving difficult to correlate individual stress responses with differences in fitness outcomes. This review summarizes the challenge of making broad generalized assumptions about fitness consequences of the stress response given the functional variation we observe.