Sex-specific maternal programming of corticosteroid-binding globulin by predator odour.

Predation is a key organizing force in ecosystems. The threat of predation may act to programme the endocrine hypothalamic-pituitary-adrenal axis during development to prepare offspring for the environment they are likely to encounter. Such effects are typically investigated through the measurement of corticosteroids (Cort). Corticosteroid-binding globulin (CBG) plays a key role in regulating the bioavailability of Cort, with only free unbound Cort being biologically active. We investigated the effects of prenatal predator odour exposure (POE) in mice on offspring CBG and its impact on Cort dynamics before, during and after restraint stress in adulthood. POE males, but not females, had significantly higher serum CBG at baseline and during restraint and lower circulating levels of Free Cort. Restraint stress was associated with reduced liver transcript abundance of SerpinA6 (CBG-encoding gene) only in control males. POE did not affect SerpinA6 promoter DNA methylation. Our results indicate that prenatal exposure to a natural stressor led to increased CBG levels, decreased per cent of Free Cort relative to total and inhibited restraint stress-induced downregulation of CBG transcription. These changes suggest an adaptive response to a high predator risk environment in males but not females that could buffer male offspring from chronic Cort exposure.

The impact of variable predation risk on stress in snowshoe hares over the cycle in North America's boreal forest: adjusting to change.

The boreal forest is one of the world's ecosystems most affected by global climate warming. The snowshoe hare, its predators, and their population dynamics dominate the mammalian component of the North American boreal forest. Our past research has shown the 9-11-year hare cycle to be predator driven, both directly as virtually all hares that die are killed by their predators, and indirectly through sublethal risk effects on hare stress physiology, behavior, and reproduction. We replicated this research over the entire cycle by measuring changes in predation risk expected to drive changes in chronic stress. We examined changes in hare condition and stress axis function using a hormonal challenge protocol in the late winter of 7 years-spanning all phases of the cycle from the increase through to the low (2014-2020). We simultaneously monitored changes in hare abundance as well as those of their primary predators, lynx and coyotes. Despite observing the expected changes in hare-predator numbers over the cycle, we did not see the predicted changes in chronic stress metrics in the peak and decline phases. Thus, the comprehensive physiological signature indicative of chronic predator-induced stress seen from our previous work was not present in this current cycle. We postulate that hares may now be increasingly showing behavior-mediated rather than stress-mediated responses to their predators. We present evidence that increases in primary productivity have affected boreal community structure and function. We speculate that climate change has caused this major shift in the indirect effects of predation on hares.

Maternal effects in mammals: Broadening our understanding of offspring programming.

The perinatal period is a sensitive time in mammalian development that can have long-lasting consequences on offspring phenotype via maternal effects. Maternal effects have been most intensively studied with respect to two major conditions: maternal diet and maternal stress. In this review, we shift the focus by discussing five major additional maternal cues and their influence on offspring phenotype: maternal androgen levels, photoperiod (melatonin), microbiome, immune regulation, and milk composition. We present the key findings for each of these topics in mammals, their mechanisms of action, and how they interact with each other and with the maternal influences of diet and stress. We explore their impacts in the contexts of both predictive adaptive responses and the developmental origins of disease, identify knowledge gaps and research opportunities in the field, and place a particular emphasis on the application and consideration of these effects in non-model species and natural ecological systems.

Hair cortisol as a reliable indicator of stress physiology in the snowshoe hare: Influence of body region, sex, season, and predator-prey population dynamics.

Hair cortisol concentration is increasingly used as a convenient, non-invasive, and integrative measure of physiology and health in natural populations of mammals. However, the use of this index is potentially confounded by individual variation in body region-specific differences in cortisol deposition rates. Here we examine correlations in cortisol concentrations in hair collected from the ear, shoulder, and thigh of wild snowshoe hares, Lepus americanus, as well as the influence of sex on cortisol measurements. We further evaluated this technique's ability to capture seasonal and cyclical patterns of snowshoe hare glucocorticoid secretion from 2013 to 2015 in the southwestern Yukon (Canada). We found positive correlations (R2 = 0.20-0.32) in all pairwise comparisons among body regions, and differences among individuals accounted for the greatest proportion of variance (47.3%) in measurements. From 2013 to 2015 the hares' primary predator - Canada lynx - approximately doubled in population abundance. We found a significant increase in hare hair cortisol concentrations across this time period. Cortisol indices were higher in summer than winter pelage, reflecting predicted physiological responses to seasonal variation in food availability and individual risk. Variation in hair cortisol concentrations was more similar to long-term (weeks-months) integrative indices of adrenal capacity than point samples of fecal glucocorticoid metabolite concentrations. Overall, we find that hair cortisol analysis is a simple and useful tool for estimations of population-level stress physiology in wild mammals, and sampling of core body regions with consistent moulting patterns produced the most robust results in this species.

Integrating Ecological and Evolutionary Context in the Study of Maternal Stress.

Maternal stress can prenatally influence offspring phenotypes and there are an increasing number of ecological studies that are bringing to bear biomedical findings to natural systems. This is resulting in a shift from the perspective that maternal stress is unanimously costly, to one in which maternal stress may be beneficial to offspring. However, this adaptive perspective is in its infancy with much progress to still be made in understanding the role of maternal stress in natural systems. Our aim is to emphasize the importance of the ecological and evolutionary context within which adaptive hypotheses of maternal stress can be evaluated. We present five primary research areas where we think future research can make substantial progress: (1) understanding maternal and offspring control mechanisms that modulate exposure between maternal stress and subsequent offspring phenotype response; (2) understanding the dynamic nature of the interaction between mothers and their environment; (3) integrating offspring phenotypic responses and measuring both maternal and offspring fitness outcomes under real-life (either free-living or semi-natural) conditions; (4) empirically testing these fitness outcomes across relevant spatial and temporal environmental contexts (both pre- and post-natal environments); (5) examining the role of maternal stress effects in human-altered environments-i.e., do they limit or enhance fitness. To make progress, it is critical to understand the role of maternal stress in an ecological context and to do that, we must integrate across physiology, behavior, genetics, and evolution.

Impact of high predation risk on genome-wide hippocampal gene expression in snowshoe hares.

The population dynamics of snowshoe hares (Lepus americanus) are fundamental to the ecosystem dynamics of Canada's boreal forest. During the 8- to 11-year population cycle, hare densities can fluctuate up to 40-fold. Predators in this system (lynx, coyotes, great-horned owls) affect population numbers not only through direct mortality but also through sublethal effects. The chronic stress hypothesis posits that high predation risk during the decline severely stresses hares, leading to greater stress responses, heightened ability to mobilize cortisol and energy, and a poorer body condition. These effects may result in, or be mediated by, differential gene expression. We used an oligonucleotide microarray designed for a closely-related species, the European rabbit (Oryctolagus cuniculus), to characterize differences in genome-wide hippocampal RNA transcript abundance in wild hares from the Yukon during peak and decline phases of a single cycle. A total of 106 genes were differentially regulated between phases. Array results were validated with quantitative real-time PCR, and mammalian protein sequence similarity was used to infer gene function. In comparison to hares from the peak, decline phase hares showed increased expression of genes involved in metabolic processes and hormone response, and decreased expression of immune response and blood cell formation genes. We found evidence for predation risk effects on the expression of genes whose putative functions correspond with physiological impacts known to be induced by predation risk in snowshoe hares. This study shows, for the first time, a link between changes in demography and alterations in neural RNA transcript abundance in a natural population.