Developmental exposure of California mice to endocrine disrupting chemicals and potential effects on the microbiome-gut-brain axis at adulthood.

Xenoestrogens are chemicals found in plant products, such as genistein (GEN), and in industrial chemicals, e.g., bisphenol A (BPA), present in plastics and other products that are prevalent in the environment. Early exposure to such endocrine disrupting chemicals (EDC) may affect brain development by directly disrupting neural programming and/or through the microbiome-gut-brain axis. To test this hypothesis, California mice (Peromyscus californicus) offspring were exposed through the maternal diet to GEN (250 mg/kg feed weight) or BPA (5 mg/kg feed weight, low dose- LD or 50 mg/kg, upper dose-UD), and dams were placed on these diets two weeks prior to breeding, throughout gestation, and lactation. Various behaviors, gut microbiota, and fecal metabolome were assessed at 90 days of age. The LD but not UD of BPA exposure resulted in individuals spending more time engaging in repetitive behaviors. GEN exposed individuals were more likely to exhibit such behaviors and showed socio-communicative disturbances. BPA and GEN exposed females had increased number of metabolites involved in carbohydrate metabolism and synthesis. Males exposed to BPA or GEN showed alterations in lysine degradation and phenylalanine and tyrosine metabolism. Current findings indicate cause for concern that developmental exposure to BPA or GEN might affect the microbiome-gut-brain axis.

Body size trends in response to climate and urbanization in the widespread North American deer mouse, Peromyscus maniculatus.

Body size decline is hypothesized to be a key response to climate warming, including warming driven by urban heat islands. However, urbanization may also generate selective gradients for body size increases in smaller endotherms via habitat fragmentation. Here we utilize a densely sampled, multi-source dataset to examine how climate and urbanization affect body size of Peromyscus maniculatus (PEMA), an abundant rodent found across North America. We predicted PEMA would conform to Bergmann's Rule, e.g. larger individuals in colder climates, spatially and temporally. Hypotheses regarding body size in relation to urbanization are less clear; however, with increased food resources due to greater anthropogenic activity, we expected an increase in PEMA size. Spatial mixed-models showed that PEMA conform to Bergmann's Rule and that PEMA were shorter in more urbanized areas. With the inclusion of decade in mixed-models, we found PEMA mass, but not length, is decreasing over time irrespective of climate or population density. We also unexpectedly found that, over time, smaller-bodied populations of PEMA are getting larger, while larger-bodied populations are getting smaller. Our work highlights the importance of using dense spatiotemporal datasets, and modeling frameworks that account for bias, to better disentangle broad-scale climatic and urbanization effects on body size.

Adaptive Shifts in Gene Regulation Underlie a Developmental Delay in Thermogenesis in High-Altitude Deer Mice.

Aerobic performance is tied to fitness as it influences an animal's ability to find food, escape predators, or survive extreme conditions. At high altitude, where low O2 availability and persistent cold prevail, maximum metabolic heat production (thermogenesis) is an aerobic performance trait that is closely linked to survival. Understanding how thermogenesis evolves to enhance survival at high altitude will yield insight into the links between physiology, performance, and fitness. Recent work in deer mice (Peromyscus maniculatus) has shown that adult mice native to high altitude have higher thermogenic capacities under hypoxia compared with lowland conspecifics, but that developing high-altitude pups delay the onset of thermogenesis. This finding suggests that natural selection on thermogenic capacity varies across life stages. To determine the mechanistic cause of this ontogenetic delay, we analyzed the transcriptomes of thermoeffector organs-brown adipose tissue and skeletal muscle-in developing deer mice native to low and high altitude. We demonstrate that the developmental delay in thermogenesis is associated with adaptive shifts in the expression of genes involved in nervous system development, fuel/O2 supply, and oxidative metabolism pathways. Our results demonstrate that selection has modified the developmental trajectory of the thermoregulatory system at high altitude and has done so by acting on the regulatory systems that control the maturation of thermoeffector tissues. We suggest that the cold and hypoxic conditions of high altitude force a resource allocation tradeoff, whereby limited energy is allocated to developmental processes such as growth, versus active thermogenesis, during early development.

Ontogenesis of evolved changes in respiratory physiology in deer mice native to high altitude.

High-altitude environments are cold and hypoxic, and many high-altitude natives have evolved changes in respiratory physiology that improve O2 uptake in hypoxia as adults. Altricial mammals undergo a dramatic metabolic transition from ectothermy to endothermy in early post-natal life, which may influence the ontogenetic development of respiratory traits at high altitude. We examined the developmental changes in respiratory and haematological traits in deer mice (Peromyscus maniculatus) native to high altitude, comparing the respiratory responses to progressive hypoxia between highland and lowland deer mice. Among adults, highlanders exhibited higher total ventilation and a more effective breathing pattern (relatively deeper tidal volumes), for mice that were caught and tested at their native altitudes and those lab-raised in normoxia. Lab-raised progeny of each population were also tested at post-natal day (P)7, 14, 21 and 30. Highlanders developed an enhanced hypoxic ventilatory response by P21, concurrent with the full maturation of the carotid bodies, and their more effective breathing pattern arose by P14; these ages correspond to critical benchmarks in the full development of homeothermy in highlanders. However, highlanders exhibited developmental delays in ventilatory sensitivity to hypoxia, hyperplasia of type I cells in the carotid body and increases in blood haemoglobin content compared with lowland mice. Nevertheless, highlanders maintained consistently higher arterial O2 saturation in hypoxia across development, in association with increases in blood-O2 affinity that were apparent from birth. We conclude that evolved changes in respiratory physiology in high-altitude deer mice become expressed in association with the post-natal development of endothermy.

Developmental delay in shivering limits thermogenic capacity in juvenile high-altitude deer mice (Peromyscus maniculatus).

Many endotherms native to cold and hypoxic high-altitude (HA) environments have evolved a highly vascularized and aerobic skeletal muscle. This specialized muscle phenotype contributes via shivering to an enhanced capacity for aerobic thermogenesis (cold-induced V̇O2,max). However, it is unclear how selection at HA for shivering thermogenesis acts early in the development of small altricial mammals, which are born with immature skeletal muscles and without the capacity for homeothermic endothermy. We have previously shown that postnatal maturation of brown adipose tissue and non-shivering thermogenesis is delayed in HA native deer mouse pups (Peromyscus maniculatus). To assess whether HA adaptation has also altered the developmental program of skeletal muscle and shivering thermogenesis, we used laboratory-reared descendants of deer mice native to low altitude (LA, 430 m a.s.l.) and HA (4350 m a.s.l.) and a LA congeneric outgroup (P. leucopus). We found that LA juveniles were able to shiver robustly at 2 weeks after birth. However, HA juveniles were unlikely able to shiver at this point, resulting in a 30% lower capacity for thermoregulation compared with lowlanders. It was only at 27 days after birth that HA juveniles had established the aerobic muscle phenotype characteristic of HA adults and a superior cold-induced V̇O2,max compared with LA mice of the same age. The capacity for shivering may be delayed in HA mice to allow energy to be allocated to other important processes such as growth.

Development of homeothermic endothermy is delayed in high-altitude native deer mice (Peromyscus maniculatus).

Altricial mammals begin to independently thermoregulate during the first few weeks of postnatal development. In wild rodent populations, this is also a time of high mortality (50-95%), making the physiological systems that mature during this period potential targets for selection. High altitude (HA) is a particularly challenging environment for small endotherms owing to unremitting low O2 and ambient temperatures. While superior thermogenic capacities have been demonstrated in adults of some HA species, it is unclear if selection has occurred to survive these unique challenges early in development. We used deer mice (Peromyscus maniculatus) native to high and low altitude (LA), and a strictly LA species (Peromyscus leucopus), raised under common garden conditions, to determine if postnatal onset of endothermy and maturation of brown adipose tissue (BAT) is affected by altitude ancestry. We found that the onset of endothermy corresponds with the maturation and activation of BAT at an equivalent age in LA natives, with 10-day-old pups able to thermoregulate in response to acute cold in both species. However, the onset of endothermy in HA pups was substantially delayed (by approx. 2 days), possibly driven by delayed sympathetic regulation of BAT. We suggest that this delay may be part of an evolved cost-saving measure to allow pups to maintain growth rates under the O2-limited conditions at HA.

Increased vasopressin expression in the BNST accompanies paternally induced territoriality in male and female California mouse offspring.

While developmental consequences of parental investment on species-typical social behaviors has been extensively characterized in same-sex parent-offspring interactions, the impact of opposite-sex relationships is less clear. In the bi-parental California mouse (Peromyscus californicus), paternal retrieval behavior induces territorial aggression and the expression of arginine vasopressin (AVP) in adult male offspring. Although similar patterns of territorially emerge among females, the sexually dimorphic AVP system has not been considered since it is generally thought to regulate male-typical behavior. However, we recently demonstrated that male and female P. californicus offspring experience increases in plasma testosterone following paternal retrieval. Since AVP expression is androgen-dependent during development, we postulate that increases in AVP expression may accompany territoriality in female, as well as male offspring. To explore this aim, adult P. californicus offspring that received either high or low levels of paternal care (retrievals) during early development were tested for territoriality and immunohistochemical analysis of AVP within the bed nucleus of the stria terminalis (BNST), paraventricular nucleus (PVN), and supraoptic nucleus (SON). Consistent with previous studies, high care offspring were more aggressive than low care offspring. Moreover, high care offspring had significantly more AVP immunoreactive (AVP-ir) cells within the BNST than low care offspring. This pattern was observed within female as well as male offspring, suggesting an equally salient role for paternal care on female offspring physiology. Regardless of early social experience, sex differences in AVP persisted in the BNST, with males having greater expression than females.

Thyroid pathology in deer mice (Peromyscus maniculata) from a reclaimed mine site on the athabasca oil sands.

Information on naturally occurring thyroid disease in wild animals in general and in small mammals specifically is extremely limited. In the present field-based work, we investigated the structure and function of thyroid glands of deer mice (Peromyscus maniculata) studied as sentinels of ecosystem sustainability on reclaimed areas post-mining on the oil sands of northeastern Alberta, because of their greater sensitivity to contaminants relative to meadow voles (Microtus pennsylvanicus) on the same sites. Extraction of bitumen in the oil sands of northeastern Alberta, results in the release of contaminants including polycyclic aromatic compounds (PACs), metals, and metalloids to the environment that have a measurable biological cost to wildlife living in the affected areas. In previous investigations, deer mice exposed to pollution at reclaimed areas showed compromised ability to regenerate glutathione indicating oxidative stress, together with decreased testicular mass and body condition during the breeding season. In the present study, thyroid glands from those deer mice from the reclaimed site had markedly increased follicular cell proliferation and decreased colloid compared to animals from the reference site. This pathology was positively associated with the greater oxidative stress in the deer mice. Thyroid hormones, both thyroxine and triiodothyronine, were also higher in animals with greater oxidative stress indicating increased metabolic demands from contaminant related subclinical toxicity. This work emphasizes the value of using a combination of endocrinological, histological and oxidative stress biomarkers to provide sensitive measures of contaminant exposure in small mammals on the oil sands.

Photoperiodic regulation of behavior: Peromyscus as a model system.

Winter and summer present vastly different challenges to animals living outside of the tropics. To survive and reproduce, individuals must anticipate seasonal environmental changes and adjust physiology and behavior accordingly. Photoperiod (day length) offers a relatively 'noise free' environmental signal that non-tropical animals use to tell the time of year, and whether winter is approaching or receding. In some cases, photoperiodic signals may be fine-tuned by other proximate cues such as food availability or temperature. The pineal hormone, melatonin, is a primary physiological transducer of the photoperiodic signal. It tracks night length and provokes changes in physiology and behavior at appropriate times of the year. Because of their wide latitudinal distribution, Peromyscus has been well studied in the context of photoperiodic regulation of physiology and behavior. Here, we discuss how photoperiodic signals are transduced by pineal melatonin, how melatonin acts on target tissues, and subsequent consequences for behavior. Using a life-history paradigm involving trade-offs between the immune and reproductive systems, specific emphasis is placed on aggression, metabolism, and cognition. We discuss future directions including examining the effects of light pollution on photoperiodism, genetic manipulations to test the role of specific genes in the photoperiodic response, and using Peromyscus to test evolutionary theories of aging.

Peromyscus transcriptomics: Understanding adaptation and gene expression plasticity within and between species of deer mice.

Deer mice in the genus Peromyscus occupy nearly every terrestrial habitat in North America, and have a long history as subjects of behavioral, ecological, evolutionary, and physiological study. Recent advances in transcriptomics, the study of the complete set of RNA transcripts produced by certain cell types or under certain conditions, have contributed to the development of Peromyscus as a model system. We review the recent use of transcriptomics to investigate how natural selection and gene expression plasticity contribute to the existence of deer mice in challenging environments such as highlands, deserts, and cities across North America. Transcriptomics also holds great promise for elucidating the genetic basis of mating systems and other behaviors in Peromyscus, but has to date been underutilized for developmental biology and disease studies. Future Peromyscus studies should apply robust comparative frameworks to analyze the transcriptomics of multiple populations of the same species across varying environmental conditions, as well as multiple species that vary in traits of interest.

Factors affecting larval tick feeding success: host, density and time.

BACKGROUND: Ectoparasites rely on blood-feeding to sustain activity, support development and produce offspring. Blood-feeding is also a route for transmission of diverse vector-borne pathogens. The likelihood of successfully feeding is thus an important aspect of ectoparasite population dynamics and pathogen transmission. Factors that affect blood-feeding include ectoparasite density, host defenses, and ages of the host and ectoparasite. How these factors interact to affect feeding success is not well understood. METHODS: We monitored blood-feeding success of larval Rocky Mountain wood ticks (RMWTs; Dermacentor andersoni) on deer mice (Peromyscus maniculatus) in several experiments to determine how tick density, host defense, and ages of mice and ticks interact to influence feeding success. In the first experiment, tick-naive deer mice were infested with one of several densities of RMWT larvae, while a second cohort of mice were infested with 50 larvae each. Two weeks after ticks dropped off, mice in the first cohort were re-exposed to 50 larvae each and mice in the second cohort were re-exposed to varying densities of larvae. In the second experiment mice of different ages (45-374 days old) were exposed to 50 larvae each. Two weeks later mice were re-exposed to 50 larvae each. We combined data from these and several similar experiments to test the generality of the patterns we observed. Lastly, we tested whether tick feeding success was consistent on individual mice that were challenged on four occasions. RESULTS: Mice acquired resistance such that feeding success declined dramatically from the first to the second infestation. Feeding success also declined with tick density and tick age. Mice, however, became more permissive with age. The sizes of these effects were similar and additive. Surprisingly, over successive infestations the relative resistance among mice changed among hosts within a cohort. CONCLUSIONS: We predict that larval blood-feeding success, and thus development to the nymph stage, will change due to variation in tick age and density, as well as the age and history of the host. Incorporating these biotic factors into modeling of tick population dynamics may improve predictions of tick-borne pathogen transmission.

Repetitive motor behavior: further characterization of development and temporal dynamics.

Repetitive behaviors are diagnostic for autism spectrum disorders, common in related neurodevelopmental disorders, and normative in typical development. In order to identify factors that mediate repetitive behavior development, it is necessary to characterize the expression of these behaviors from an early age. Extending previous findings, we characterized further the ontogeny of stereotyped motor behavior both in terms of frequency and temporal organization in deer mice. A three group trajectory model provided a good fit to the frequencies of stereotyped behavior across eight developmental time points. Group based trajectory analysis using a measure of temporal organization of stereotyped behavior also resulted in a three group solution. Additionally, as the frequency of stereotyped behavior increased with age, the temporal distribution of stereotyped responses became increasingly regular or organized indicating a strong association between these measures. Classification tree and principal components analysis showed that accurate classification of trajectory group could be done with fewer observations. This ability to identify trajectory group membership earlier in development allows for examination of a wide range of variables, both experiential and biological, to determine their impact on altering the expected trajectory of repetitive behavior across development. Such studies would have important implications for treatment efforts in neurodevelopmental disorders such as autism.

Retinal cone photoreceptors of the deer mouse Peromyscus maniculatus: development, topography, opsin expression and spectral tuning.

A quantitative analysis of photoreceptor properties was performed in the retina of the nocturnal deer mouse, Peromyscus maniculatus, using pigmented (wildtype) and albino animals. The aim was to establish whether the deer mouse is a more suitable model species than the house mouse for photoreceptor studies, and whether oculocutaneous albinism affects its photoreceptor properties. In retinal flatmounts, cone photoreceptors were identified by opsin immunostaining, and their numbers, spectral types, and distributions across the retina were determined. Rod photoreceptors were counted using differential interference contrast microscopy. Pigmented P. maniculatus have a rod-dominated retina with rod densities of about 450.000/mm(2) and cone densities of 3000-6500/mm(2). Two cone opsins, shortwave sensitive (S) and middle-to-longwave sensitive (M), are present and expressed in distinct cone types. Partial sequencing of the S opsin gene strongly supports UV sensitivity of the S cone visual pigment. The S cones constitute a 5-15% minority of the cones. Different from house mouse, S and M cone distributions do not have dorsoventral gradients, and coexpression of both opsins in single cones is exceptional (<2% of the cones). In albino P. maniculatus, rod densities are reduced by approximately 40% (270.000/mm(2)). Overall, cone density and the density of cones exclusively expressing S opsin are not significantly different from pigmented P. maniculatus. However, in albino retinas S opsin is coexpressed with M opsin in 60-90% of the cones and therefore the population of cones expressing only M opsin is significantly reduced to 5-25%. In conclusion, deer mouse cone properties largely conform to the general mammalian pattern, hence the deer mouse may be better suited than the house mouse for the study of certain basic cone properties, including the effects of albinism on cone opsin expression.

Prediction of Peromyscus maniculatus (deer mouse) population dynamics in Montana, USA, using satellite-driven vegetation productivity and weather data.

Deer mice (Peromyscus maniculatus) are the main reservoir host for Sin Nombre virus, the primary etiologic agent of hantavirus pulmonary syndrome in North America. Sequential changes in weather and plant productivity (trophic cascades) have been noted as likely catalysts of deer mouse population irruptions, and monitoring and modeling of these phenomena may allow for development of early-warning systems for disease risk. Relationships among weather variables, satellite-derived vegetation productivity, and deer mouse populations were examined for a grassland site east of the Continental Divide and a sage-steppe site west of the Continental Divide in Montana, USA. We acquired monthly deer mouse population data for mid-1994 through 2007 from long-term study sites maintained for monitoring changes in hantavirus reservoir populations, and we compared these with monthly bioclimatology data from the same period and gross primary productivity data from the Moderate Resolution Imaging Spectroradiometer sensor for 2000-06. We used the Random Forests statistical learning technique to fit a series of predictive models based on temperature, precipitation, and vegetation productivity variables. Although we attempted several iterations of models, including incorporating lag effects and classifying rodent density by seasonal thresholds, our results showed no ability to predict rodent populations using vegetation productivity or weather data. We concluded that trophic cascade connections to rodent population levels may be weaker than originally supposed, may be specific to only certain climatic regions, or may not be detectable using remotely sensed vegetation productivity measures, although weather patterns and vegetation dynamics were positively correlated.

Small mammals collected from a site with elevated selenium concentrations and three reference sites.

Small mammals were trapped in July, August, and September 1999 at Kesterson Reservoir (Merced County, CA), a site with elevated concentrations of selenium (Se), and at three nearby reference sites. Deer mice (Peromyscus maniculatus) were the most frequently trapped species at all of the sites, and western harvest mice (Reithrodontomys megalotis) and house mice (Mus musculus) were also trapped frequently. About half the animals collected from the reference sites were in reproductive condition, compared to less than a quarter of the animals from Kesterson. A lower proportion of the deer mice trapped at Kesterson was male, compared to about half at the reference sites. Deer mice from Kesterson also tended to have a lower condition index (body weight/body length) than those from the reference sites. Mice from Kesterson had enlarged livers, based on a higher liver-to-body-weight ratio (% liver). Male mice from Kesterson tended to have a smaller anogenital distance than male mice from reference sites, suggesting some feminization of Kesterson mice. Mice from Kesterson had higher liver Se concentrations than mice from reference sites, and some mice from reference sites had surprisingly low liver Se concentrations. It is possible that the effects observed were caused by physical stressors at Kesterson such as lower water and food availability but it also suggests that long-term exposure to elevated levels of Se may be, in part, the cause of some of the differences observed in small mammals from Kesterson.

The interaction of parasites and resources cause crashes in a wild mouse population.

1. Populations of white-footed mice Peromyscus leucopus and deer mice Peromyscus maniculatus increase dramatically in response to food availability from oak acorn masts. These populations subsequently decline following this resource pulse, but these crashes cannot be explained solely by resource depletion, as food resources are still available as population crashes begin. 2. We hypothesized that intestinal parasites contribute to these post-mast crashes; Peromyscus are infected by many intestinal parasites that are often transmitted by density-dependent contact and can cause harm to their hosts. To test our hypothesis, we conducted a factorial experiment in natural populations by supplementing food to mimic a mast and by removal of intestinal nematodes with the drug, ivermectin. 3. Both food supplementation and the removal of intestinal nematodes lessened the rate and magnitude of the seasonal population declines as compared with control populations. However, the combination of food supplementation and removal of intestinal nematodes prevented seasonal population crashes entirely. 4. We also showed a direct effect on the condition of individuals. Faecal corticosterone levels, an indicator of the stress response, were significantly reduced in populations receiving both food supplementation and removal of intestinal nematodes. This effect was observed in autumn, before the overwinter crash observed in control populations, which may indicate that stress caused by the combination of food limitation and parasite infection is a physiological signal that predicts low winter survival and reproduction. 5. This study is one of the few to demonstrate that the interaction between resource availability and infectious disease is important for shaping host population dynamics and emphasizes that multiple factors may drive oscillations in wild animal populations.

Population dynamics of a generalist rodent in relation to variability in pulsed food resources in a fragmented landscape.

1. Pulsed food resources are often considered equivalent in their potential impact on the reproduction and population dynamics of consumers, but differences in the attributes of food pulses and their distribution in the landscape may cause differences in their effects. 2. We tested whether a perishable pulsed resource (periodical cicadas, Magicicada spp.) had similar effects on the population dynamics of a generalist forest rodent, Peromyscus leucopus, as have been reported for a cacheable pulsed resource (acorn mast). 3. Because the availability of periodical cicadas may vary between edge and interior habitat, we also tested whether habitat type (edge vs. interior) and fragment size affected the abundance of cicadas and P. leucopus. 4. Nearly 90% of the variation in the relative population densities of P. leucopus was explained by the variation in the relative densities of periodical cicadas, and fragments with more cicadas tended to have more reproductive female mice and litters. 5. We found more cicadas and more P. leucopus in edge than interior habitat, but no differences in the relative densities of either in relation to fragment size. 6. Data from a non-emergence year revealed no differences other than the presence of periodical cicadas that could explain the 50% higher relative densities of P. leucopus in the emergence year. 7. At the beginning of the emergence of periodical cicadas, the three fragments with the highest numbers of emergence holes had three times more mice than the fragments with the lowest numbers of emergence holes, suggesting that P. leucopus is able to anticipate the emergence of periodical cicadas and increase reproduction prior to the pulse. 8. Hence, despite differences in perishability, seasonal timing and nutritional quality of pulsed food resources in a fragmented landscape, they appear to have similar positive effects on the population dynamics of the generalist rodent, P. leucopus and, in fact, P. leucopus may be able to anticipate resource pulses.

Heavy metal exposure, reproductive activity, and demographic patterns in white-footed mice (Peromyscus leucopus) inhabiting a contaminated floodplain wetland.

We examined the concentrations of selected metals and selenium (Se) in the tissues of white-footed mice (Peromyscus leucopus) collected at a constructed wetland originally created as a retention basin for sediments dredged from Lake DePue, Illinois. These sediments were contaminated with high concentrations of cadmium (Cd), zinc (Zn), and other elements as a result of nearby smelting operations. White-footed mice inhabiting the former retention basin experienced greater exposure to Cd, Pb, and Se than those from nearby reference sites. Concentrations of Cu and Zn in livers of mice from the contaminated wetland and adjacent floodplain reference site were greater than in mice from the more-distant reference sites. Judging by concentrations in their kidneys, white-footed mice inhabiting the floodplain adjacent to the contaminated wetland had greater exposure to Cd than those from the two more-distant reference sites. Concentrations of Hg in tissues of mice did not vary appreciably among sites. Concentrations of Cd and Se in the tissues of some white-footed mice from the contaminated wetland exceeded critical concentrations observed in experimental studies of laboratory mice and rats; with few exceptions tissue Pb concentrations were below published effects levels. However, we did not detect changes in abundance, demographics, or reproductive activity that might suggest population-level effects of contaminant exposure. Mean weight of embryos expressed as a function of crown-rump length did not differ among locations sampled, and no gross lesions indicative of exposure to heavy metals were observed. Kidney and liver weight, corrected for body weight, were nominally, though not significantly, lowest in both male and female mice from areas of increased Cd and Pb exposure. Metals dredged from Lake DePue were still bioavailable 25 years after deposition. However, small mammal populations are resilient to environmental stressors and we did not detect differences in population parameters suggesting that the population of white-footed mice inhabiting the contaminated wetland was at risk from increased exposure to these contaminants.

Development partly determines the aerobic performance of adult deer mice, Peromyscus maniculatus.

Previous studies suggest that genetic factors and acclimation can account for differences in aerobic performance (V(O(2)max)) between high and low altitude populations of small mammals. However, it remains unclear to what extent development at different oxygen partial pressures (P(O(2))) can affect aerobic performance during adulthood. Here we compared the effects of development at contrasting altitudes versus effects of acclimation during adulthood on V(O(2)max). Two groups of deer mice were born and raised for 5 weeks at one of two altitudes (340 and 3800 m above sea level). Then, a subset of each group was acclimated to the opposite altitude for 8 weeks. We measured V(O(2)max) for each individual in hypoxia (P(O(2))=13.5 kPa, 14% O(2) at 3800 m) and normoxia (P(O(2))=20.4 kPa, 21% O(2) at 340 m) to control for P(O(2)) effects. At 5 weeks of age, high altitude born mice attained significantly higher V(O(2)max) than low altitude born mice (37.1% higher in hypoxia and 72.1% higher in normoxia). Subsequently, deer mice acclimated for 8 weeks to high altitude had significantly higher V(O(2)max) regardless of their birth site (21.0% and 72.9% difference in hypoxia and normoxia, respectively). A significant development x acclimation site interaction comparing V(O(2)max) in hypoxia and normoxia at 13 weeks of age suggests that acclimation effects depend on development altitude. Thus, reversible plasticity during adulthood cannot fully compensate for developmental effects on aerobic performance. We also found that differences in aerobic performance in previous studies may have been underestimated if animals from contrasting altitudes were measured at different P(O(2)).