Thyroid hormone links environmental signals to DNA methylation.

Environmental conditions experienced within and across generations can impact individual phenotypes via so-called 'epigenetic' processes. Here we suggest that endocrine signalling acts as a 'sensor' linking environmental inputs to epigenetic modifications. We focus on thyroid hormone signalling and DNA methylation, but other mechanisms are likely to act in a similar manner. DNA methylation is one of the most important epigenetic mechanisms, which alters gene expression patterns by methylating cytosine bases via DNA methyltransferase enzymes. Thyroid hormone is mechanistically linked to DNA methylation, at least partly by regulating the activity of DNA methyltransferase 3a, which is the principal enzyme that mediates epigenetic responses to environmental change. Thyroid signalling is sensitive to natural and anthropogenic environmental impacts (e.g. light, temperature, endocrine-disrupting pollution), and here we propose that thyroid hormone acts as an environmental sensor to mediate epigenetic modifications. The nexus between thyroid hormone signalling and DNA methylation can integrate multiple environmental signals to modify phenotypes, and coordinate phenotypic plasticity at different time scales, such as within and across generations. These dynamics can have wide-ranging effects on health and fitness of animals, because they influence the time course of phenotypic adjustments and potentially the range of environmental stimuli that can elicit epigenetic responses. This article is part of the theme issue 'Endocrine responses to environmental variation: conceptual approaches and recent developments'.

Endocrine responses to environmental variation.

Hormones regulate most physiological functions and life history from embryonic development to reproduction. In addition to their roles in growth and development, hormones also mediate responses to the abiotic, social and nutritional environments. Hormone signalling is responsive to environmental changes to adjust phenotypes to prevailing conditions. Both hormone levels and receptor densities can change to provide a flexible system of regulation. Endocrine flexibility connects the environment to organismal function, and it is central to understanding environmental impacts and their effect on individuals and populations. Hormones may also act as a 'sensor' to link environmental signals to epigenetic processes and thereby effect phenotypic plasticity within and across generations. Many environmental parameters are now changing in unprecedented ways as a result of human activity. The knowledge base of organism-environmental interactions was established in environments that differ in many ways from current conditions as a result of ongoing human impacts. It is an urgent contemporary challenge to understand how evolved endocrine responses will modulate phenotypes in response to anthropogenic environmental impacts including climate change, light-at-night and chemical pollution. Endocrine responses play a central role in ecology, and their integration into conservation can lead to more effective outcomes. This article is part of the theme issue 'Endocrine responses to environmental variation: conceptual approaches and recent developments'.

Intergenerational plasticity aligns with temperature-dependent selection on offspring metabolic rates.

Metabolic rates are linked to key life-history traits that are thought to set the pace of life and affect fitness, yet the role that parents may have in shaping the metabolism of their offspring to enhance survival remains unclear. Here, we investigated the effect of temperature (24°C or 30°C) and feeding frequency experienced by parent zebrafish (Danio rerio) on offspring phenotypes and early survival at different developmental temperatures (24°C or 30°C). We found that embryo size was larger, but survival lower, in offspring from the parental low food treatment. Parents exposed to the warmer temperature and lower food treatment also produced offspring with lower standard metabolic rates-aligning with selection on embryo metabolic rates. Lower metabolic rates were correlated with reduced developmental and growth rates, suggesting selection for a slow pace of life. Our results show that intergenerational phenotypic plasticity on offspring size and metabolic rate can be adaptive when parent and offspring temperatures are matched: the direction of selection on embryo size and metabolism aligned with intergenerational plasticity towards lower metabolism at higher temperatures, particularly in offspring from low-condition parents. These findings provide evidence for adaptive parental effects, but only when parental and offspring environments match. This article is part of the theme issue 'The evolutionary significance of variation in metabolic rates'.

New horizons for comparative studies and meta-analyses.

Comparative analyses and meta-analyses are key tools to elucidate broad biological principles, yet the two approaches often appear different in purpose. We propose an integrated approach that can generate deeper insights into ecoevolutionary processes. Marrying comparative and meta-analytic approaches will allow for (i) a more accurate investigation of drivers of biological variation, (ii) a greater ability to account for sources of non-independence in experimental data, (iii) more effective control of publication bias, and (iv) improved transparency and reproducibility. Stronger integration of meta-analytic and comparative studies can also broaden the scope from species-centric investigations to community-level responses and function-valued traits (e.g., reaction norms). We illuminate commonalities, differences, and the transformative potential of combining these methodologies for advancing ecology and evolutionary biology.

Warming and pollution interact to alter energy transfer efficiency, performance and fitness across generations in zebrafish (Danio rerio).

Energy transfer efficiency across different trophic levels, from food to new biomass, can determine population dynamics and food-web function. Here we show that the energy needed to produce a unit of new biomass increases with warming and exposure to bisphenol A (BPA), an endocrine disrupting compound. These environmental effects are at least partially transmitted across generations via DNA methylation. We raised parental (F0) and their offspring (F1) zebrafish (Danio rerio) of two genotypes (DNA methyltransferase 3a knock-out [DNMT3a-/-] and wild type [DNMT3a+/+]) at different temperatures (24 and 30 °C), with and without BPA (0 and 10 µg l-1) to test whether the effects of BPA are i) temperature specific, ii) mediated by DNA methylation, and iii) transmitted across generations even if offspring are not exposed. All experimental factors interacted to influence growth in length and mass, and metabolic rates with the result that wild-type F0 and F1 fish experienced the greatest energetic cost of growth under warm conditions in the presence of BPA. However, this response was not observed in DNMT3a-/- fish, indicating that DNA methylation is at least partly responsible for mediating these effects. Under the same conditions (warm + BPA) wild-type parents had reduced swimming performance, and reduced fecundity, and offspring embryonic survival was reduced significantly; genotype affected these responses significantly. Our results indicate that the conditions that are becoming increasingly common globally - warming and endocrine disrupting compounds from plastic pollution and production - can have detrimental effects on energy transfer efficiency and thereby potentially on food-web structure. These effects can be transmitted across generations even if offspring are not exposed to the pollutant, and are likely to have ramifications for conservation and fisheries.

Feeding frequency does not interact with BPA exposure to influence metabolism or behaviour in zebrafish (Danio rerio).

Resource limitation can constrain energy (ATP) production, and thereby affect locomotion and behaviour such as exploration of novel environments and boldness. Consequently, ecological processes such as dispersal and interactions within and between species may be influenced by food availability. Energy metabolism, and behaviour are regulated by endocrine signalling, and may therefore be impacted by endocrine disrupting compounds (EDCs) including bisphenol A (BPA) derived from plastic manufacture and pollution. It is important to determine the impacts of these novel environmental contexts to understand how human activity alters individual physiology and behaviour and thereby populations. Our aim was to determine whether BPA exposure interacts with feeding frequency to alter metabolism and behaviour. In a fully factorial experiment, we show that low feeding frequency reduced zebrafish (Danio rerio) mass, condition, resting metabolic rates, total distance moved and speed in a novel arena, as well as anxiety indicated by the number of times fish returned to a dark shelter. However, feeding frequency did not significantly affect maximal metabolic rates, aerobic scope, swimming performance, latency to leave a shelter, or metabolic enzyme activities (citrate synthase and lactate dehydrogenase). Natural or anthropogenic fluctuation in food resources can therefore impact energetics and movement of animals with repercussions for ecological processes such as dispersal. BPA exposure reduced LDH activity and body mass, but did not interact with feeding frequency. Hence, behaviour of adult fish is relatively insensitive to disruption by BPA. However, alteration of LDH activity by BPA could disrupt lactate metabolism and signalling and together with reduction in body mass could affect size-dependent reproductive output. BPA released by plastic manufacture and pollution can thereby impact conservation and management of natural resources.

How can physiology best contribute to wildlife conservation in a warming world?

Global warming is now predicted to exceed 1.5°C by 2033 and 2°C by the end of the 21st century. This level of warming and the associated environmental variability are already increasing pressure on natural and human systems. Here we emphasize the role of physiology in the light of the latest assessment of climate warming by the Intergovernmental Panel on Climate Change. We describe how physiology can contribute to contemporary conservation programmes. We focus on thermal responses of animals, but we acknowledge that the impacts of climate change are much broader phylogenetically and environmentally. A physiological contribution would encompass environmental monitoring, coupled with measuring individual sensitivities to temperature change and upscaling these to ecosystem level. The latest version of the widely accepted Conservation Standards designed by the Conservation Measures Partnership includes several explicit climate change considerations. We argue that physiology has a unique role to play in addressing these considerations. Moreover, physiology can be incorporated by institutions and organizations that range from international bodies to national governments and to local communities, and in doing so, it brings a mechanistic approach to conservation and the management of biological resources.

Sex-specific transgenerational plasticity: developmental temperatures of mothers and fathers have different effects on sons and daughters.

Each parent can influence offspring phenotype via provisioning of the zygote or sex-specific DNA methylation. Transgenerational plasticity may therefore depend on the environmental conditions experienced by each parent. We tested this hypothesis by conducting a fully factorial experiment across three generations of guppies (Poecilia reticulata), determining the effects of warm (28°C) and cold (21°C) thermal backgrounds of mothers and fathers on mass and length, and thermal performance (sustained and sprint swimming speeds, citrate synthase and lactate dehydrogenase activities; 18, 24, 28, 32 and 36°C test temperatures) of sons and daughters. Offspring sex was significant for all traits except for sprint speed. Warmer mothers produced sons and daughters with reduced mass and length, and warmer fathers produced shorter sons. Sustained swimming speed (Ucrit) of male offspring was greatest when both parents were raised at 28°C, and warmer fathers produced daughters with greater Ucrit. Similarly, warmer fathers produced sons and daughters with greater metabolic capacity. We show that the thermal variation experienced by parents can modify offspring phenotype, and that predicting the impacts of environmental change on populations would require knowledge of the thermal background of each mother and father, particularly where sexes are spatially segregated.

Biological mechanisms matter in contemporary wildlife conservation.

Given limited resources for wildlife conservation paired with an urgency to halt declines and rebuild populations, it is imperative that management actions are tactical and effective. Mechanisms are about how a system works and can inform threat identification and mitigation such that conservation actions that work can be identified. Here, we call for a more mechanistic approach to wildlife conservation and management where behavioral and physiological tools and knowledge are used to characterize drivers of decline, identify environmental thresholds, reveal strategies that would restore populations, and prioritize conservation actions. With a growing toolbox for doing mechanistic conservation research as well as a suite of decision-support tools (e.g., mechanistic models), the time is now to fully embrace the concept that mechanisms matter in conservation ensuring that management actions are tactical and focus on actions that have the potential to directly benefit and restore wildlife populations.

Bisphenol S reduces locomotor performance and modifies muscle protein levels but not mitochondrial bioenergetics in adult zebrafish.

Human activity has now introduced novel chemicals into most aquatic ecosystems. Endocrine-disrupting compounds originating from plastic pollution and manufacture can have pronounced biological effects by disrupting hormone-mediated processes. Bisphenol A (BPA) is one of the most commonly produced endocrine-disrupting compounds, which interferes with signalling by a broad range of hormones. In recognition of its potentially harmful effects, BPA is being replaced by substitutes such as bisphenol S (BPS). However, toxicological studies revealed that BPS too can bind to hormone receptors and disrupt signalling, particularly of thyroid hormone. The aim of this study was to test whether BPS exposure impacts locomotor performance and muscle function in zebrafish (Danio rerio). Locomotor performance depends on thyroid hormone signalling, and it is closely related to fitness so that its disruption can have negative ecological and evolutionary consequences. BPS exposure of 15 µg l-1 [∼60 nM] and 30 µg l-1 (but not 60 µg l-1) decreased sustained swimming performance (Ucrit), but not sprint speed. In a fully factorial design, we show that living in flowing water increased Ucrit compared to a still water control, and that BPS reduced Ucrit under both conditions but did not eliminate the training effect. In a second factorial experiment, we show that BPS did not affect mitochondrial bioenergetics in skeletal muscle (state 3 and 4 rates, respiratory control ratios, ROS production), but that induced hypothyroidism decreased state 3 and 4 rates of respiration. However, both hypothyroidism and BPS exposure decreased activity of AMP-activated protein kinase (pAMPK:total AMPK) but increased protein levels of myocyte enhancer factor 2, and slow and fast myosin heavy chains. Our data indicate that BPS is not a safe alternative for BPA and that exposure to BPS can have ecological consequences, which are likely to be at least partly mediated via thyroid hormone disruption.

Can animals tune tissue mechanics in response to changing environments caused by anthropogenic impacts?

Anthropogenic climate change and pollution are impacting environments across the globe. This Review summarises the potential impact of such anthropogenic effects on animal tissue mechanics, given the consequences for animal locomotor performance and behaviour. More specifically, in light of current literature, this Review focuses on evaluating the acute and chronic effects of temperature on the mechanical function of muscle tissues. For ectotherms, maximal muscle performance typically occurs at temperatures approximating the natural environment of the species. However, species vary in their ability to acclimate to chronic changes in temperature, which is likely to have longer-term effects on species range. Some species undergo periods of dormancy to avoid extreme temperature or drought. Whilst the skeletal muscle of such species generally appears to be adapted to minimise muscle atrophy and maintain performance for emergence from dormancy, the increased occurrence of extreme climatic conditions may reduce the survival of individuals in such environments. This Review also considers the likely impact of anthropogenic pollutants, such as hormones and heavy metals, on animal tissue mechanics, noting the relative paucity of literature directly investigating this key area. Future work needs to determine the direct effects of anthropogenic environmental changes on animal tissues and related changes in locomotor performance and behaviour, including accounting for currently unknown interactions between environmental factors, e.g. temperature and pollutants.

Interactive effects of anthropogenic environmental drivers on endocrine responses in wildlife.

Anthropogenic activity has created unique environmental drivers, which may interact to produce unexpected effects. My aim was to conduct a systematic review of the interactive effects of anthropogenic drivers on endocrine responses in non-human animals. The interaction between temperature and light can disrupt reproduction and growth by impacting gonadotropins, thyroid hormones, melatonin, and growth hormone. Temperature and endocrine disrupting compounds (EDCs) interact to modify reproduction with differential effects across generations. The combined effects of light and EDCs can be anxiogenic, so that light-at-night could increase anxiety in wildlife. Light and noise increase glucocorticoid release by themselves, and together can modify interactions between individuals and their environment. The literature detailing interactions between drivers is relatively sparse and there is a need to extend research to a broader range of taxa and interactions. I suggest that incorporating endocrine responses into Adverse Outcome Pathways would be beneficial to improve predictions of environmental effects.

Variations in cost of transport and their ecological consequences: a review.

Movement is essential in the ecology of most animals, and it typically consumes a large proportion of individual energy budgets. Environmental conditions modulate the energetic cost of movement (cost of transport, COT), and there are pronounced differences in COT between individuals within species and across species. Differences in morphology affect COT, but the physiological mechanisms underlying variation in COT remain unresolved. Candidates include mitochondrial efficiency and the efficiency of muscle contraction-relaxation dynamics. Animals can offset increased COT behaviourally by adjusting movement rate and habitat selection. Here, we review the theory underlying COT and the impact of environmental changes on COT. Increasing temperatures, in particular, increase COT and its variability between individuals. Thermal acclimation and exercise can affect COT, but this is not consistent across taxa. Anthropogenic pollutants can increase COT, although few chemical pollutants have been investigated. Ecologically, COT may modify the allocation of energy to different fitness-related functions, and thereby influence fitness of individuals, and the dynamics of animal groups and communities. Future research should consider the effects of multiple stressors on COT, including a broader range of pollutants, the underlying mechanisms of COT and experimental quantifications of potential COT-induced allocation trade-offs.

Bisphenols impact hormone levels in animals: A meta-analysis.

Bisphenols are used in the manufacture of plastics and are endocrine disrupting compounds detectable in free living organisms and environments globally. The original bisphenol, bisphenol A (BPA), is best known as a xenoestrogen, but it also disrupts other steroid hormones and other classes of hormones including thyroid and pituitary hormones. When its toxicity became better known, BPA was replaced by presumably less toxic alternatives, including bisphenols S, F, and AF. However, recent data suggest that all bisphenols can have endocrine disrupting effects, although their impacts remain unresolved particularly in non-human animals. Our aim was to establish the current state-of-knowledge of the effects of different bisphenols on circulating hormone levels in non-human animals. Our meta-analysis showed that a diverse range of hormones (including thyroid hormones, corticosterone, follicle stimulating hormone, luteinizing hormone, and estradiol) are strongly impacted by exposure to any bisphenol type, and that in laboratory rats (Rattus norvegicus) the effect was modified by life-stage. Although there were qualitative differences, BPA alternatives had as great or greater effects on hormone levels as BPA. However, data coverage across hormones was uneven, and most studies measured the effects of BPA on vertebrate reproductive hormones. Similarly, taxonomic coverage was poor. Over 80% of data originated from laboratory rats and zebrafish (Danio rerio) and there are no data for whole classes of invertebrates and vertebrates (e.g., amphibians). Our results show that all bisphenols alter circulating levels of a broad range of hormones. However, the current state-of-knowledge is incomplete so that the ecological impacts of bisphenols are difficult to gauge, although based on the available data bisphenols are likely to be detrimental to a broad range of taxa and ecosystems.

Evolution of plasticity: metabolic compensation for fluctuating energy demands at the origin of life.

Phenotypic plasticity of physiological functions enables rapid responses to changing environments and may thereby increase the resilience of organisms to environmental change. Here, we argue that the principal hallmarks of life itself, self-replication and maintenance, are contingent on the plasticity of metabolic processes ('metabolic plasticity'). It is likely that the Last Universal Common Ancestor (LUCA), 4 billion years ago, already possessed energy-sensing molecules that could adjust energy (ATP) production to meet demand. The earliest manifestation of metabolic plasticity, switching cells from growth and storage (anabolism) to breakdown and ATP production (catabolism), coincides with the advent of Darwinian evolution. Darwinian evolution depends on reliable translation of information from information-carrying molecules, and on cell genealogy where information is accurately passed between cell generations. Both of these processes create fluctuating energy demands that necessitate metabolic plasticity to facilitate replication of genetic material and (proto)cell division. We propose that LUCA possessed rudimentary forms of these capabilities. Since LUCA, metabolic networks have increased in complexity. Generalist founder enzymes formed the basis of many derived networks, and complexity arose partly by recruiting novel pathways from the untapped pool of reactions that are present in cells but do not have current physiological functions (the so-called 'underground metabolism'). Complexity may thereby be specific to environmental contexts and phylogenetic lineages. We suggest that a Boolean network analysis could be useful to model the transition of metabolic networks over evolutionary time. Network analyses can be effective in modelling phenotypic plasticity in metabolic functions for different phylogenetic groups because they incorporate actual biochemical regulators that can be updated as new empirical insights are gained.

Physiology can predict animal activity, exploration, and dispersal.

Physiology can underlie movement, including short-term activity, exploration of unfamiliar environments, and larger scale dispersal, and thereby influence species distributions in an environmentally sensitive manner. We conducted meta-analyses of the literature to establish, firstly, whether physiological traits underlie activity, exploration, and dispersal by individuals (88 studies), and secondly whether physiological characteristics differed between range core and edges of distributions (43 studies). We show that locomotor performance and metabolism influenced individual movement with varying levels of confidence. Range edges differed from cores in traits that may be associated with dispersal success, including metabolism, locomotor performance, corticosterone levels, and immunity, and differences increased with increasing time since separation. Physiological effects were particularly pronounced in birds and amphibians, but taxon-specific differences may reflect biased sampling in the literature, which also focussed primarily on North America, Europe, and Australia. Hence, physiology can influence movement, but undersampling and bias currently limits general conclusions.

Rates of warming impact oxidative stress in zebrafish (Danio rerio).

Potentially negative effects of thermal variation on physiological functions may be modulated by compensatory responses, but their efficacy depends on the time scale of phenotypic adjustment relative to the rate of temperature change. Increasing temperatures in particular can affect mitochondrial bioenergetics and rates of reactive oxygen species (ROS) production. Our aim was to test whether different rates of temperature increase affect mitochondrial bioenergetics and modulate oxidative stress. We exposed zebrafish (Danio rerio) to warming from 20°C to 28°C over 3, 6, 24 or 48 h, and compared these with a control group that was kept at constant 20°C. Fish exposed to the fastest (3 h) and slowest (48 h) rates of warming had significantly higher rates of H2O2 production relative to the control treatment, and the proportion of O2 converted to H2O2 (H2O2/O2 ratio) was significantly greater in these groups. However, ROS production was not paralleled by differences in mitochondrial substrate oxidation rates, leak respiration rates or coupling (respiratory control ratios). Increased rates of ROS production did not lead to damage of proteins or membranes, which may be explained by a moderate increase in catalase activity at the fastest, but not the slowest, rate of warming. The increase in ROS production at the slowest rate of warming indicates that even seemingly benign environments may be stressful. Understanding how animals respond to different rates of temperature change is important, because the rate determines the time period for phenotypic adjustments and it also alters the environmental thermal signal that triggers compensatory pathways.

Endocrine disruption from plastic pollution and warming interact to increase the energetic cost of growth in a fish.

Energetic cost of growth determines how much food-derived energy is needed to produce a given amount of new biomass and thereby influences energy transduction between trophic levels. Growth and development are regulated by hormones and are therefore sensitive to changes in temperature and environmental endocrine disruption. Here, we show that the endocrine disruptor bisphenol A (BPA) at an environmentally relevant concentration (10 µgl-1) decreased fish (Danio rerio) size at 30°C water temperature. Under the same conditions, it significantly increased metabolic rates and the energetic cost of growth across development. By contrast, BPA decreased the cost of growth at cooler temperatures (24°C). BPA-mediated changes in cost of growth were not associated with mitochondrial efficiency (P/O ratios (i.e. adenosine diphosphate (ADP) used/oxygen consumed) and respiratory control ratios) although BPA did increase mitochondrial proton leak. In females, BPA decreased age at maturity at 24°C but increased it at 30°C, and it decreased the gonadosomatic index suggesting reduced investment into reproduction. Our data reveal a potentially serious emerging problem: increasing water temperatures resulting from climate warming together with endocrine disruption from plastic pollution can impact animal growth efficiency, and hence the dynamics and resilience of animal populations and the services these provide.

Physiological Performance Curves: When Are They Useful?

This review serves as an introduction to a special issue of Frontiers in Physiology, focused on the importance of physiological performance curves across phylogenetic and functional boundaries. Biologists have used performance curves to describe the effects of changing environmental conditions on animal physiology since the late 1800s (at least). Animal physiologists have studied performance curves extensively over the past decades, and there is a good foundation to understanding how the environment affects physiological functions of individuals. Our goal here was to build upon this research and address outstanding questions regarding the mutability and applicability of performance curves across taxonomic groups and levels of biological organization. Performance curves are not fixed at a taxonomic, population, or individual level - rather they are dynamic and can shift in response to evolutionary pressures (e.g., selection) and epigenetic programming (e.g., plasticity). The mechanisms underlying these shifts are being increasingly used to predict the efficacy with which plasticity and heritability of performance curves can render individuals and populations less vulnerable to climate change. Individual differences in physiological performance curves (and plasticity of performance curves) can also have cascading effects at higher levels of biological organization. For instance, individual physiology likely influences group behaviors in non-additive ways. There is a need therefore to extend the concept of performance curves to social interactions and sociality. Collectively, this special issue emphasizes the power of how within- and between-individual shifts in performance curves might scale up to the population-, species-, and community-level dynamics that inform conservation management strategies.