Early-life Environmental Conditions Research Articles

Ectoparasite presence and brood size manipulation interact to accelerate telomere shortening in nestling jackdaws.

Early-life conditions impact fitness, but whether the combined effect of extrinsic stressors is additive or synergistic is not well known. This is a major knowledge gap because exposure to multiple stressors is frequent. Telomere dynamics may be instrumental when testing how stressors interact because many factors affect telomere shortening, and telomere shortening predicts survival. We evaluated the effect of manipulated brood size and natural infestation by the carnid fly Carnus hemapterus on nestling growth and telomere shortening of wild jackdaws (Corvus monedula). Telomere length, measured in blood using TRF, shortened on average by 264 bp, and on average, Carnus infection induced more telomere shortening. Further analyses showed that in enlarged broods, nestlings' telomeres shortened more when parasitized, while in reduced broods there was no effect of infection on telomere shortening. We conclude that there is a synergistic effect of number of siblings and Carnus infection on telomere shortening rate: blood-sucking parasites may negatively impact telomeres by increasing cell proliferation and/or physiological stress, and coping with infection may be less successful in enlarged broods with increased sibling competition. Larger nestlings had shorter telomeres independent of age, brood manipulation or infection. Growth was independent of infestation but in enlarged broods, nestlings were lighter at fledging. Our findings indicate that (i) evaluating consequences of early-life environmental conditions in isolation may not yield a full picture due to synergistic effects, and (ii) effects of environmental conditions may be cryptic, for example, on telomeres, with fitness consequences expressed beyond the temporal framework of the study.

Glucocorticoid receptor expression in blood, but not across brain regions, reveals long-term effects of early life adversity in zebra finches

Early-life environment can affect organisms for life on many levels. The glucocorticoid receptor (GR) gene has a pivotal role mediating organismal physiological and behavioral responses to environmental change, and is sensitive to early-life environmental conditions and epigenetic programming. Longitudinal studies require non-lethal sampling of peripheral tissues (e.g. blood), but this approach is dependent on the extent to which GR expression in peripheral tissues covaries with GR expression in central tissues. To test for the long-term effects of early life adversity on GR expression across brain and peripheral tissues, we manipulated developmental conditions of captive zebra finches (n = 45), rearing them in either benign or harsh conditions through manipulation of parental foraging costs. We measured relative GR mRNA expression in blood and five brain regions in adulthood: hippocampus, hypothalamus, amygdala, ventral striatum, and the nidopallium caudolaterale (analogous to the mammalian prefrontal cortex), using qPCR. We further tested whether GR expression was modulated by natal brood size (which affected growth), age at sampling, and sex. GR expression correlations among tissues varied widely in magnitude and direction, ranging from -0.27 to +0.80, indicating that our understanding of developmental effects on GR expression and associated phenotypes needs to be region specific rather than organism wide. A more consistent pattern was that GR expression increased with age in blood, ventral striatum and hippocampus; GR expression was independent of age in other tissues. Developmental treatment did not affect GR expression in any of the tissues measured directly, but in blood and ventral striatum of adult females we found a positive correlation between nestling mass and GR expression. Thus, GR expression in blood was affected by early life conditions as reflected in growth in adult females, a pattern also found in one brain tissue, but not ubiquitous across brain regions. These results point at sex-dependent physiological constraints during development, shaping early life effects on GR expression in females only. Further study is required to investigate whether these tissue-dependent effects more generally reflect tissue-dependent long-term effects of early life adversity. This, together with investigating the physiological consequences of GR expression levels on individual performance and coping abilities, will be fundamental towards understanding the mechanisms mediating long-term impacts of early life, and the extent to which these can be quantified through non-lethal sampling.

Early-life food stress hits females harder than males in insects: A meta-analysis of sex differences in environmental sensitivity.

Fitness consequences of early-life environmental conditions are often sex-specific, but corresponding evidence for invertebrates remains inconclusive. Here, we use meta-analysis to evaluate sex-specific sensitivity to larval nutritional conditions in insects. Using literature-derived data for 85 species with broad phylogenetic and ecological coverage, we show that females are generally more sensitive to food stress than males. Stressful nutritional conditions during larval development typically lead to female-biased mortality and thus increasingly male-biased sex ratios of emerging adults. We further demonstrate that the general trend of higher sensitivity to food stress in females can primarily be attributed to their typically larger body size in insects and hence higher energy needs during development. By contrast, there is no consistent evidence of sex-biased sensitivity in sexually size-monomorphic species. Drawing conclusions regarding sex-biased sensitivity in species with male-biased size dimorphism remains to wait for the accumulation of relevant data. Our results suggest that environmental conditions leading to elevated juvenile mortality may potentially affect the performance of insect populations further by reducing the proportion of females among individuals reaching reproductive age. Accounting for sex-biased mortality is therefore essential to understanding the dynamics and demography of insect populations, not least importantly in the context of ongoing insect declines.

Sex differences in glycolipidic disorders after exposure to maternal hyperglycemia during early development.

The aim of this review was to summarize sex differences in glycolipid metabolic phenotypes of human and animal models after exposure to maternal hyperglycemia and overview the underlying mechanisms, providing a new perspective on the maternal hyperglycemia-triggered risk of glycolipidic disorders in offspring. A comprehensive literature search within PubMed was performed. Selected publications related to studies on offspring exposed to maternal hyperglycemia investigating the sex differences of glycolipid metabolism were reviewed. Maternal hyperglycemia increases the risk of glycolipid metabolic disorders in offspring, such as obesity, glucose intolerance and diabetes. Whether with or without intervention, metabolic phenotypes have been shown to exhibit sex differences between male and female offspring in response to maternal hyperglycemia, which may be related to gonadal hormones, organic intrinsic differences, placenta, and epigenetic modifications. Sex may play a role in the different incidences and pathogenesis of abnormal glycolipid metabolism. More studies investigating both sexes are needed to understand how and why environmental conditions in early life affect long-term health between male and female individuals.

Genotype-by-environment interactions modulate the rate of microevolution in reproductive timing in humans.

Evidence from natural populations shows that changes in environmental conditions can cause rapid modifications in the evolutionary potential of phenotypes, partly through genotype-by-environment interactions (G×E). Therefore, the overall rate of microevolution should depend on fluctuations in environmental conditions, even when directional selection is sustained over several generations. We tested this hypothesis in a preindustrial human population that experienced a microevolutionary change in age at first reproduction (AFR) of mothers, using the annual infant mortality rate (IMR) as an indicator of environmental conditions during their early life. Using quantitative genetics analyses, we found that G×Es explained a nonnegligible fraction of the additive genetic variance in AFR and in relative fitness, as well as of the genetic covariance between AFR and fitness (i.e., the Robertson-Price covariance). The covariance was stronger for individuals exposed to unfavorable early-life environmental conditions. Our results unravel the presence of G×Es in an important life history trait and its impact on the rate of microevolution, which appears to have been sensitive to short-term fluctuations in local environmental conditions.

Early-life conditions, height and mortality of nineteenth-century Dutch vagrant women

ABSTRACT Adult height is a remarkably accurate summary of early-life environmental conditions. Because of that, height may be negatively associated with mortality. These relationships – between early-life conditions and height, and between height and mortality – have been well-studied in modern samples of both genders, and in historical samples of men. However, these relationships are understudied historical samples of women. Therefore, this study aimed to better-understand the determinants and consequences of female adult height. More specifically, this study examined the relationships between (1) early-life environmental conditions and adult height, and (2) adult height and mortality. To accomplish this, we used a unique dataset that provided lifetime information of 1,088 women who were born between 1811 and 1838, and who were convicted of vagrancy and sent to the penal colonies of Veenhuizen and de Ommerschans. An ordered logistic regression was used to assess the relationship between early-life determinants and adult height. Cox regression analyses were performed to investigate the relationship between height and mortality. In terms of findings, region of birth, population size of municipality at birth, parental socio-economic status and religion were associated with adult height. The results examining height’s relationship to mortality were more surprising: taller vagrant women – those more than one standard deviation above the mean height – had higher probabilities of dying earlier than those within 0.5 standard deviations of the mean height. Ultimately, this study adds to the evidence that taller height is likely not universally beneficial for living longer.

Maternal deprivation effect on morphine-induced CPP is related to changes in opioid receptors in selected rat brain regions (hippocampus, prefrontal cortex, and nucleus accumbens)

Early-life environmental conditions affect offspring's development. Maternal deprivation (MD) can induce persistent changes that give rise to neuropsychiatric diseases including substance abuse disorders. However, long-lasting mechanisms that determine vulnerability to drug addiction remain unknown. We hypothesized that MD could induce changes in Opioid system, HPA (hypothalamic-pituitary-adrenal) axis, and BDNF (brain-derived neurotrophic factor), so may be involved in the drug abuse in later life. Male offspring of Wistar rats (n = 8 per group) were subjected to 3 h of daily MD during postnatal days 1–14. In adulthood, morphine-induced CPP (conditioned place preference) was investigated using two doses of morphine (3 and 5 mg/kg). Serum corticosterone level was measured by ELISA method. The expression level of genes in selected brain regions (hippocampus, prefrontal cortex, and nucleus accumbens) was determined by qPCR (quantitative PCR). A greater morphine-induced CPP was observed in MD rats with 3 and 5 mg/kg morphine compared to controls. MD group had a higher corticosterone level. A significant decrease was observed in the expression of BDNF gene (in all of the selected brain regions) and GR (glucocorticoid receptor) gene (in the hippocampus and nucleus accumbens) in MD rats. Also, a significant increase in the expression of μ Opioid receptor (in all of the selected brain regions) and κ Opioid receptor (in the prefrontal cortex and nucleus accumbens) was observed in MD rats. Our results suggest that MD induces alterations in the HPA axis function, BDNF level, and Opioid receptors system that enhance vulnerability to morphine at adulthood.

Early-life seasonal, weather and social effects on telomere length in a wild mammal.

Early-life environmental conditions can provide a source of individual variation in life-history strategies and senescence patterns. Conditions experienced in early life can be quantified by measuring telomere length, which can act as a biomarker of survival probability in some species. Here, we investigate whether seasonal changes, weather conditions and group size are associated with early-life and/or early-adulthood telomere length in a wild population of European badgers (Meles meles). We found substantial intra-annual changes in telomere length during the first 3years of life, where within-individual effects showed shorter telomere lengths in the winter following the first spring and a trend for longer telomere lengths in the second spring compared to the first winter. In terms of weather conditions, cubs born in warmer, wetter springs with low rainfall variability had longer early-life (3-12months old) telomeres. Additionally, cubs born in groups with more cubs had marginally longer early-life telomeres, providing no evidence of resource constraint from cub competition. We also found that the positive association between early-life telomere length and cub survival probability remained when social and weather variables were included. Finally, after sexual maturity, in early adulthood (i.e., 12-36months) we found no significant association between same-sex adult group size and telomere length (i.e., no effect of intrasexual competition). Overall, we show that controlling for seasonal effects, which are linked to food availability, is important in telomere length analyses, and that variation in telomere length in badgers reflects early-life conditions and also predicts first year cub survival.

Early-Life Corticosterone Body Condition Influence Social Status and Survival in a Food-Caching Passerine.

Individuals undergo profound changes throughout their early life as they grow and transition between life-history stages. As a result, the conditions that individuals experience during development can have both immediate and lasting effects on their physiology, behavior, and, ultimately, fitness. In a population of Canada jays in Algonquin Provincial Park, Ontario, Canada, we characterized the diet composition and physiological profile of young jays at three key time points during development (nestling, pre-fledge, and pre-dispersal) by quantifying stable-carbon (δ13C) and -nitrogen (δ15N) isotopes and corticosterone concentrations in feathers. We then investigated the downstream effects of early-life diet composition, feather corticosterone, and environmental conditions on a juvenile's social status, body condition, and probability of being observed in the fall following hatch. Across the three time points, the diet of Canada jay young was composed primarily of vertebrate tissue and human food with the proportion of these food items increasing as the jays neared dispersal. Feather corticosterone concentrations also shifted across the three time points, decreasing from nestling to pre-dispersal. Dominant juveniles had elevated corticosterone concentrations in their feathers grown pre-dispersal compared with subordinates. High body condition as nestlings was associated with high body condition as juveniles and an increased probability of being observed in the fall. Together, our results demonstrate that nestling physiology and body condition influence the social status and body condition once individuals are independent, with potential long-term consequences on survival and fitness.

Do Early-Life Conditions Drive Variation in Senescence of Female Bighorn Sheep?

The rate of senescence may vary among individuals of a species according to individual life histories and environmental conditions. According to the principle of allocation, changes in mortality driven by environmental conditions influence how organisms allocate resources among costly functions. In several vertebrates, environmental conditions during early life impose trade-offs in allocation between early reproduction and maintenance. The effects of conditions experienced during early life on senescence, however, remain poorly documented in wild populations. We examined how several early-life environmental conditions affected reproductive and survival senescence in wild bighorn sheep. We found long-term effects of high population density at birth, precipitations during the winter before birth, and temperature during the winter following birth that decreased survival after 7 years of age. High temperature during the first summer and autumn of life and high Pacific decadal oscillation decreased reproductive success at old ages. However, harsh early-life environment did not influence the rate of senescence in either survival or reproduction. Contrary to our expectation, we found no trade-off between reproductive allocation prior to senescence and senescence. Our results do show that early-life environmental conditions are important drivers of later survival and reproductive success and contribute to intra-specific variation in late-life fitness, but not aging patterns. These conditions should therefore be considered when studying the mechanisms of senescence and the determinants of variation in both survival and reproductive senescence at older ages.

Telomere attrition rates are associated with weather conditions and predict productive lifespan in dairy cattle

Telomere length is predictive of adult health and survival across vertebrate species. However, we currently do not know whether such associations result from among-individual differences in telomere length determined genetically or by early-life environmental conditions, or from differences in the rate of telomere attrition over the course of life that might be affected by environmental conditions. Here, we measured relative leukocyte telomere length (RLTL) multiple times across the entire lifespan of dairy cattle in a research population that is closely monitored for health and milk production and where individuals are predominantly culled in response to health issues. Animals varied in their change in RLTL between subsequent measurements and RLTL shortened more during early life and following hotter summers which are known to cause heat stress in dairy cows. The average amount of telomere attrition calculated over multiple repeat samples of individuals predicted a shorter productive lifespan, suggesting a link between telomere loss and health. TL attrition was a better predictor of when an animal was culled than their average TL or the previously for this population reported significant TL at the age of 1 year. Our present results support the hypothesis that TL is a flexible trait that is affected by environmental factors and that telomere attrition is linked to animal health and survival traits. Change in telomere length may represent a useful biomarker in animal welfare studies.

Grow fast, die young? The causes and consequences of adult height and prolonged growth in nineteenth century Maastricht.

Both adult body height and the developmental growth trajectory have been found to be important predictors of later-life mortality. However, evidence for these relationships largely comes from contemporary populations, where most people live until old-age. It is an open question how height and growth impact later-life mortality in a population where death before old-age is more common. We therefore study the causes and mortality consequences of height and growth in a high-mortality, nineteenth-century Dutch population. We exploit a unique dataset from three sources: conscription records with late-adolescent height, standing militia registers with adult height, and individual cause-of-death and age-at-death information. Our study is set in the Dutch city of Maastricht. To determine the causes of height and growth (either early-life environmental conditions or shared family inheritance), we use Pearson's correlation tests and multilevel linear models. To determine height and growth's consequences, we use survival analyses, for all-cause mortality and cause-specific mortality. Regarding the causes of height and growth, we find that prolonged growth and adolescent height are more strongly associated with external environmental factors than shared family inheritance. Adult height is more strongly related to shared family inheritance. Regarding the consequences of height and growth, we find that being taller in adulthood and growing faster are significantly associated with an increased hazard of death for the all-cause mortality model. While we find the 'usual suspects' for the causes of height and growth, our findings for the consequences are surprising: the tallest individuals who grow the fastest have the highest hazard of death. Our results may be explained by a selection effect: the tall, fast growers may be the least-selected in early-life, and are therefore more vulnerable than their peers in adulthood.

Individual-based population genomics reveal different drivers of adaptation in sympatric fish

Connectivity and local adaptation are two contrasting evolutionary forces highly influencing population structure. To evaluate the impact of early-life traits and environmental conditions on genetic structuring and adaptation, we studied two sympatric fish species in the Western Mediterranean Sea: Symphodus tinca and S. ocellatus. We followed an individual-based approach and measured early-life history traits from otolith readings, gathered information on environmental variables and obtained genome-wide markers from genotyping-by-sequencing (GBS). The two species presented contrasting population structure across the same geographic gradient, with high and significant population differentiation in S. ocellatus, mostly determined by oceanographic fronts, and low differentiation and no front effect in S. tinca. Despite their different levels of genetic differentiation, we identified in both species candidate regions for local adaptation by combining outlier analysis with environmental and phenotypic association analyses. Most candidate loci were associated to temperature and productivity in S. ocellatus and to temperature and turbulence in S. tinca suggesting that different drivers may determine genomic diversity and differentiation in each species. Globally, our study highlights that individual-based approach combining genomic, environmental and phenotypic information is key to identify signals of selection and the processes mediating them.

Early-life hypoxia alters adult physiology and reduces stress resistance and lifespan in Drosophila.

In many animals, short-term fluctuations in environmental conditions in early life often exert long-term effects on adult physiology. In Drosophila, one ecologically relevant environmental variable is hypoxia. Drosophila larvae live on rotting, fermenting food rich in microorganisms, an environment characterized by low ambient oxygen. They have therefore evolved to tolerate hypoxia. Although the acute effects of hypoxia in larvae have been well studied, whether early-life hypoxia affects adult physiology and fitness is less clear. Here, we show that Drosophila exposed to hypoxia during their larval period subsequently show reduced starvation stress resistance and shorter lifespan as adults, with these effects being stronger in males. We find that these effects are associated with reduced whole-body insulin signaling but elevated TOR kinase activity, a manipulation known to reduce lifespan. We also identify a sexually dimorphic effect of larval hypoxia on adult nutrient storage and mobilization. Thus, we find that males, but not females, show elevated levels of lipids and glycogen. Moreover, we see that both males and females exposed to hypoxia as larvae show defective lipid mobilization upon starvation stress as adults. These data demonstrate how early-life hypoxia can exert persistent, sexually dimorphic, long-term effects on Drosophila adult physiology and lifespan.

Silver spoon effects are constrained under extreme adult environmental conditions.

Early-life environmental conditions may generate cohort differences in individual fitness, subsequently affecting population growth rates. Three, nonmutually exclusive hypotheses predict the nature of these fitness differences: (1) silver spoon effects, where individuals born in good conditions perform better across the range of adult environments; (2) the "environmental saturation" hypothesis, where fitness differences only occur in intermediate adult environmental conditions; and (3) the "environmental matching" or "predictive adaptive response" (PAR) hypothesis, where fitness is highest when adult environmental conditions match those experienced in early life. We quantified the context-dependent effect of early-life environment on subsequent reproductive success, survival, and population growth rate (λ) of Svalbard reindeer, and explored how well it was explained by the three hypotheses. We found that good early-life conditions increased reproductive success compared to poor early-life conditions, but only when experiencing intermediate adult environmental conditions. This is the first example of what appears to be both "beneficial" and "detrimental environmental saturation" in a natural system. Despite weak early-life effects on survival, cohorts experiencing good early-life conditions contributed to higher population growth rates, when simulating realistic variation in adult environmental conditions. Our results show how the combination of a highly variable environment and biological constraints on fitness components can suppress silver spoon effects at both extremes of the adult environmental gradient.

Individual variation in early-life telomere length and survival in a wild mammal.

Individual variation in survival probability due to differential responses to early-life environmental conditions is important in the evolution of life histories and senescence. A biomarker allowing quantification of such individual variation, and which links early-life environmental conditions with survival by providing a measure of conditions experienced, is telomere length. Here, we examined telomere dynamics among 24 cohorts of European badgers (Meles meles). We found a complex cross-sectional relationship between telomere length and age, with no apparent loss over the first 29months, but with both decreases and increases in telomere length at older ages. Overall, we found low within-individual consistency in telomere length across individual lifetimes. Importantly, we also observed increases in telomere length within individuals, which could not be explained by measurement error alone. We found no significant sex differences in telomere length, and provide evidence that early-life telomere length predicts lifespan. However, while early-life telomere length predicted survival to adulthood (≥1 year old), early-life telomere length did not predict adult survival probability. Furthermore, adult telomere length did not predict survival to the subsequent year. These results show that the relationship between early-life telomere length and lifespan was driven by conditions in early-life, where early-life telomere length varied strongly among cohorts. Our data provide evidence for associations between early-life telomere length and individual life history, and highlight the dynamics of telomere length across individual lifetimes due to individuals experiencing different early-life environments.

Adult body height as a mediator between early-life conditions and socio-economic status: the case of the Dutch Potato Famine, 1846–1847

Adult body height appears to be a relatively accurate summary variable of early-life exposures’ influence on health, and may be a useful indicator of health in populations where more traditional health-related indicators are lacking. In particular, previous studies have shown a strong, positive relationship between environmental conditions in early life (particularly nutritional availability and the disease environment) and adult height. Research has also demonstrated positive associations between height and socioeconomic status. We therefore hypothesize that height mediates the relationship between early-life conditions and later-life socio-economic outcomes. We also hypothesize that the period of exposure in early life matters, and that conditions during pregnancy or the first years of life and/or the years during puberty have the largest effects on height and socio-economic status. To test these relationships, we use a sample of 1817 Dutch military conscripts who were exposed during early life to the Dutch Potato Famine (1846–1847). We conduct mediation analyses using structural equation modelling, and test seven different time periods in early-life. We use potato prices and real wages to proxy early-life environmental conditions, and occupational status (using the HISCAM scale) to proxy socioeconomic status. We find no evidence of mediation, partial or full, in any models. However, there are significant relationships between potato prices in adolescence, height and socio-economic status. To determine causality in these relationships, further research is needed.

Non-genetic inheritance via the male germline in mammals.

Numerous studies in humans and in animal models have demonstrated that exposure to adverse environmental conditions in early life results in long-term structural and functional changes in an organism, increasing the risk of cardiometabolic, neurobehavioural and reproductive disorders in later life. Such effects are not limited to the first generation offspring but may be transmitted to a second or a number of subsequent generations, through non-genomic mechanisms. While the transmission of ‘programmed’ effects through the maternal line could occur as a consequence of multiple influences, for example, altered maternal physiology, the inheritance of effects through the male line is more difficult to explain and there is much interest in a potential role for transgenerational epigenetic inheritance. In this review, we will discuss the mechanisms by which induced effects may be transmitted through the paternal lineage, with a particular focus on the role of epigenetic inheritance.This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine’.

Early-Life Assets in Oldest-Old Age: Evidence From Primary Care Reform in Early Twentieth Century Sweden

Do early-life effects of investments in public health persist to the oldest-old ages? This article answers this question by using the primary care reform in rural Sweden that between 1890 and 1917 led to the establishment of local health districts, together with openings of hospitals and recruitments of medical personnel, as a natural experiment in early-life environmental conditions. The initiatives undertaken within these districts targeted control of infectious diseases, including various isolation and disinfection measures. This study applies a difference-in-differences method combined with propensity score matching to register-based individual-level data for Sweden from 1968 to 2012 and to multisource, purposely collected data on the reform implementation. Providing pioneering evidence for such a distal relationship (ages 78–95), this study finds that treatment through primary care in the year of birth leads to a significant reduction in all-cause mortality (4 % to 6%) and mortality from cardiovascular diseases (5 % to 6 %) and to an increase in average incomes (2 % to 3 %). The effects are universal and somewhat stronger among individuals from poor socioeconomic backgrounds and at higher baseline levels of disease burden.

Developmental Tuning of Epigenetic Clock.

Research in the field of gerontology has traditionally focused on later life stages. There is increasing evidence, however, that both the rate of age-related functional decline and the later-life health status can be programmed during early development. The central role of epigenetic mechanisms (methylation of DNA, histone modifications and regulation by non-coding RNAs) in mediating these long-term effects has been elucidated. Both rate and direction of age-associated change of epigenetic patterns (“epigenetic drift”) were shown to be largely dependent on early-life environmental conditions. Inter-individual divergences in epigenetic profiles may arise following the stochastic errors in maintaining epigenetic marks, but they may also be adaptively mediated by specific environmental cues. Recent cohort studies indicate that ticking rate of epigenetic clock, estimated by a DNA methylation-based methods, may be developmentally adjusted, and that individual’s discrepancies among epigenetic and chronological age would be likely programmed early in development. In this Perspective article, recent findings suggesting the importance of early-life determinants for life-course dynamics of epigenetic drift are summarized and discussed.