Stress Responses In Offspring Research Articles

The impact of parental and developmental stress on DNA methylation in the avian hypothalamic-pituitary-adrenal axis.

The hypothalamic-pituitary-adrenal (HPA) axis coordinates an organism's response to environmental stress. The responsiveness and sensitivity of an offspring's stress response may be shaped not only by stressors encountered in their early post-natal environment but also by stressors in their parent's environment. Yet, few studies have considered how stressors encountered in both of these early life environments may function together to impact the developing HPA axis. Here, we manipulated stressors in the parental and post-natal environments in a population of house sparrows (Passer domesticus) to assess their impact on changes in DNA methylation (and corresponding gene expression) in a suite of genes within the HPA axis. We found that nestlings that experienced early life stress across both life-history periods had higher DNA methylation in a critical HPA axis gene, the glucocorticoid receptor (NR3C1). In addition, we found that the life-history stage when stress was encountered impacted some genes (HSD11B1, NR3C1 and NR3C2) differently. We also found evidence for the mitigation of parental stress by post-natal stress (in HSD11B1 and NR3C2). Finally, by assessing DNA methylation in both the brain and blood, we were able to evaluate cross-tissue patterns. While some differentially methylated regions were tissue-specific, we found cross-tissue changes in NR3C2 and NR3C1, suggesting that blood is a suitable tissue for assessing DNA methylation as a biomarker of early life stress. Our results provide a crucial first step in understanding the mechanisms by which early life stress in different life-history periods contributes to changes in the epigenome of the HPA axis.

Intergenerational plasticity to cycling high temperature and hypoxia affects offspring stress responsiveness and tolerance in zebrafish.

Predicted climate change-induced increases in heat waves and hypoxic events will have profound effects on fishes, yet the capacity of parents to alter offspring phenotype via non-genetic inheritance and buffer against these combined stressors is not clear. This study tested how prolonged adult zebrafish exposure to combined diel cycles of thermal stress and hypoxia affect offspring early survival and development, parental investment of cortisol and heat shock proteins (HSPs), larval offspring stress responses, and both parental and offspring heat and hypoxia tolerance. Parental exposure to the combined stressor did not affect fecundity, but increased mortality, produced smaller embryos and delayed hatching. The combined treatment also reduced maternal deposition of cortisol and increased embryo hsf1, hsp70a, HSP70, hsp90aa and HSP90 levels. In larvae, basal cortisol levels did not differ between treatments, but acute exposure to combined heat stress and hypoxia increased cortisol levels in control larvae with no effect on larvae from exposed parents. In contrast, whereas larval basal hsf1, hsp70a and hsp90aa levels differed between parental treatments, the combined acute stressor elicited similar transcriptional responses across treatments. Moreover, the combined acute stressor only induced a marked increase in HSP47 levels in the larvae derived from exposed parents. Finally, combined hypoxia and elevated temperatures increased both thermal and hypoxia tolerance in adults and conferred an increase in offspring thermal but not hypoxia tolerance. These results demonstrate that intergenerational acclimation to combined thermal stress and hypoxia elicit complex carryover effects on stress responsiveness and offspring tolerance with potential consequences for resilience.

ECR Spotlight - Michael Lim.

ECR Spotlight is a series of interviews with early-career authors from a selection of papers published in Journal of Experimental Biology and aims to promote not only the diversity of early-career researchers (ECRs) working in experimental biology during our centenary year, but also the huge variety of animals and physiological systems that are essential for the 'comparative' approach. Michael Lim is an author on ' Intergenerational plasticity to cycling high temperature and hypoxia affects offspring stress responsiveness and tolerance in zebrafish', published in JEB. Michael conducted the research described in this article while a PhD candidate in Dr Nicholas J. Bernier's lab at the University of Guelph, Canada, investigating the impacts of anthropogenic activities on animals, and how research can improve our ability to understand and mitigate the effects.

The response to stressors in adulthood depends on the interaction between prenatal exposure to glucocorticoids and environmental context

Maternal stress during reproduction can influence how offspring respond to stress later in life. Greater lifetime exposure to glucocorticoid hormones released during stress is linked to greater risks of behavioral disorders, disease susceptibility, and mortality. The immense variation in individual’s stress responses is explained, in part, by prenatal glucocorticoid exposure. To explore the long-term effects of embryonic glucocorticoid exposure, we injected Japanese quail (Coturnix japonica) eggs with corticosterone. We characterized the endocrine stress response in offspring and measured experienced aggression at three different ages. We found that prenatal glucocorticoid exposure affected (1) the speed at which the stress response was terminated suggesting dysregulated negative feedback, (2) baseline corticosterone levels in a manner dependent on current environmental conditions with higher levels of experienced aggression associated with higher levels of baseline corticosterone, (3) the magnitude of an acute stress response based on baseline concentrations. We finish by proposing a framework that can be used to test these findings in future work. Overall, our findings suggest that the potential adaptive nature of prenatal glucocorticoid exposure is likely dependent on environmental context and may also be tempered by the negative effects of longer exposure to glucocorticoids each time an animal faces a stressor.

Biological and Psychological Stress Responses in Offspring of Parents Recently Diagnosed With Cancer

Biological and Psychological Stress Responses in Offspring of Parents Recently Diagnosed With Cancer

Distinct behavior in early life stress dams predicts heterogeneity in future stress response in offspring over lifespan

IntroductionExposure to early life stress (ELS) strongly predicts prevalent, impairing, and costly psychiatric illness throughout life including mental disorders. The reason, some individuals are more vulnerable to ELS whereas others remain resilient, is poorly understood. There is a need for better understanding of early biological changes triggered by ELS with responsibility to negative outcomes in health.ObjectivesWe stratify animals after ELS according to corticosterone levels. [1] Re-challenging the animals to a second stressor, chronic social defeat (CSD) [2], in adulthood was performed to understand individual trajectories depending on corticosterone exposure during early adverse conditions.MethodsWe performed ELS as previously reported [1]. Behavior of mothers was observed during ELS. Correlation between level of corticosterone and behavior observed in dams. ELS animals were exposed to a second stress in adulthood. A battery of tests for different behavioral domains was performed. Behavioral analyses was combined with assessment of litter HPA system reactivity and observed behavior in dams.ResultsStress dams where significantly higher in number of sorties over whole observation period, time dams spent outside the nest differed. We could correlate the number of sorties on p3 with corticosterone plasma level at p9. Control dams spent significantly more time outside in 9pm recordings than stress animals. We could show reduced interaction with social juvenile targets in sociability test for CSD mice. Light dark transition was significantly higher for control mice compared to CSD but lower for control vs ELS animals.ConclusionsBehavior in dams during ELS correlates with chronic stress coping mechanisms in offspring’s adulthood.DisclosureNo significant relationships.

Maternal exposure to bisphenol S induces neuropeptide signaling dysfunction and oxidative stress in the brain, and abnormal social behaviors in zebrafish (Danio rerio) offspring

Recent studies show that bisphenol S (BPS) induces multiple adverse effects in exposed organisms; however, the maternal effects of BPS exposure remain poorly understood. Here, we expose adult female zebrafish to environmentally relevant concentrations of BPS (0, 1, 10, 30 μg/L) and 1 μg/L of 17-β-estradiol (E2) as a positive control for 60 days. Females were then paired with BPS-unexposed males and their offspring were raised in control water for 6 months. Maternal exposure to BPS was found to alter social behavior and anxiety response in a dose-specific manner in male offspring. Group preferences and social cohesion were significantly reduced by maternal exposure to 1 and 10 μg/L BPS, respectively. Additionally, maternal exposure to 1 and 30 μg/L BPS and E2 decreased offspring stress responses during the novel tank test. The impaired social behavior was associated with elevated arginine-vasotocin (AVT) level as well as with the altered expression of genes involved in AVT signaling pathway (AVT, avpr1aa) and enzymatic antioxidant genes (cat and Mn-sod) in the brain. Collectively, these results suggest that maternal exposure to environmentally relevant concentrations of BPS alters social behavior in zebrafish offspring, which is likely mediated by oxidative stress and disruption of neuropeptide signaling pathways in the brain.

Developmental costs associated with early maternal withdrawal.

Neglect is the most prevalent form of maltreatment, but it has been understudied relative to abuse. Additionally, developmental outcomes associated with early maternal withdrawal have been understudied relative to outcomes associated with harsh treatment. However, a large body of studies on rodents has documented the causal effect of low maternal care on altered stress responses in offspring. Other evidence from human studies links early maternal withdrawal to clinical levels of neglect. Studies of both rodents and humans suggest that, rather than the aversive responses (e.g., fight, flight, freeze) modeled in relation to threat of attack or harsh treatment, early maternal withdrawal is associated with increased calling and contact seeking to mothers. Moreover, two longitudinal studies indicate that early maternal withdrawal, but not negative‐intrusive interaction, contributes to adolescent borderline psychopathology. The field needs prospective studies with well‐operationalized constructs of maternal withdrawal to delineate the distinct developmental pathways that may be associated with neglect.

P.0556 Distinct behavior in early life stress dams predicts heterogeneity in future stress response in offspring over lifespan

Previous studies have shown that Roux-en-Y gastric bypass (RYGB) leads to rapid regression of obesity and type 2 diabetes (T2D). However, the underlying mechanism remains unclear. This study aimed to investigate the effect of RYGB on serum lipopolysaccharide (LPS), interleukin (IL)-1, IL-6, tumor necrosis factor alpha (TNF-α), and cecal microbiota in obese rats with T2D.Obese Sprague-Dawley rats with T2D were randomly divided into RYGB diabetes operation (DO; n = 8), diabetes sham operation (DS; n = 8), and diabetic control (DC; n = 8) groups. Healthy Sprague-Dawley rats were grouped as normal control (NC; n = 8). Fasting plasma glucose and body weight were measured. The levels of peripheral serum LPS, IL-1, IL-6, and TNF-α were measured by enzyme-linked immunosorbent assay. The rats were sacrificed 12 wk after operation. Subsequently, a superior mesenteric venous blood sample was taken to measure serum LPS levels by enzyme-linked immunosorbent assay. The cecal contents of the DO and DS groups were taken to extract metagenomic DNA per the genomic DNA standardization procedure. The V4 region of the 16 S rRNA was sequenced with the Illumina Hiseq sequencing platform to compare the structure and relative abundance of cecal microbiota between the DO and DS groups.Twelve weeks after operation in the DO group, fasting plasma glucose and body weight showed a significant decrease (P < 0.05). Moreover, the levels of peripheral serum LPS, IL-1, IL-6, and TNF-α were obviously decreased (P < 0.05). A change in the LPS level of superior mesenteric venous blood also revealed a dramatic decrease (P < 0.05). Additionally, RYGB resulted in a shift of cecal microbiota in obese rats with T2D.Hypoglycemic effects after RYGB may be associated with improved levels of LPS, IL-1, IL-6, and TNF-α. Changes in the structure of cecal microbiota may also play an important role.

Maternal age and maternal environment affect stress reactivity and measures of social behaviour in laying hens

Maternal effects can shape the phenotypes of offspring, but the extent to which a layer breeder’s experience can affect commercial laying hens remains unclear. We aimed to investigate the effects of maternal age and maternal environment on laying hens’ behaviour and stress response. In our first experiment (E1), commercial hybrid hens were reared either in aviary or barren brooding cages, then housed in aviary, conventional cages or furnished (enriched) cages, thus forming different maternal housing treatments. Hens from each treatment were inseminated at three ages, and measures of response to manual restraint and social stress were assessed in offspring. In experiment 2 (E2), maternal age effects on offsprings' stress response were further investigated using fertile eggs from commercial breeder flocks at three ages. In E1, maternal age affected struggling and corticosterone during manual restraint, feather pecking and pulling and comb wounds. Additionally, maternal rearing and housing in aviary systems showed positive effects on measures of behaviour and stress response in offspring. Effects of maternal age were not replicated in E2, possibly due to methodological differences or higher tolerance to maternal effects in commercial breeders. Overall, we recommend researchers report parent stock age to increase comparison across studies and thus our understanding of maternal age effects.

Maternal glucocorticoids have minimal effects on HPA axis activity and behavior of juvenile wild North American red squirrels.

As a response to environmental cues, maternal glucocorticoids (GCs) may trigger adaptive developmental plasticity in the physiology and behavior of offspring. In North American red squirrels (Tamiasciurus hudsonicus), mothers exhibit increased GCs when conspecific density is elevated, and selection favors more aggressive and perhaps more active mothers under these conditions. We tested the hypothesis that elevated maternal GCs cause shifts in offspring behavior that may prepare them for high-density conditions. We experimentally elevated maternal GCs during gestation or early lactation. We measured two behavioral traits (activity and aggression) in weaned offspring using standardized behavioral assays. Because maternal GCs may influence offspring hypothalamic-pituitary-adrenal (HPA) axis dynamics, which may in turn affect behavior, we also measured the impact of our treatments on offspring HPA axis dynamics (adrenal reactivity and negative feedback), and the association between offspring HPA axis dynamics and behavior. Increased maternal GCs during lactation, but not gestation, slightly elevated activity levels in offspring. Offspring aggression and adrenal reactivity did not differ between treatment groups. Male, but not female, offspring from mothers treated with GCs during pregnancy exhibited stronger negative feedback compared with those from control mothers, but there were no differences in negative feedback between lactation treatment groups. Offspring with higher adrenal reactivity from mothers treated during pregnancy (both controls and GC-treated) exhibited lower aggression and activity. These results suggest that maternal GCs during gestation or early lactation alone may not be a sufficient cue to produce substantial changes in behavioral and physiological stress responses in offspring in natural populations.

Early life adversity targets the transcriptional signature of hippocampal NG2+ glia and affects voltage gated sodium (Nav) channels properties

The precise mechanisms underlying the detrimental effects of early life adversity (ELA) on adult mental health remain still elusive. To date, most studies have exclusively targeted neuronal populations and not considered neuron-glia crosstalk as a crucially important element for the integrity of stress-related brain function. Here, we have investigated the impact of ELA, in the form of a limited bedding and nesting material (LBN) paradigm, on a glial subpopulation with unique properties in brain homeostasis, the NG2+ cells. First, we have established a link between maternal behavior, activation of the offspring's stress response and heterogeneity in the outcome to LBN manipulation. We further showed that LBN targets the hippocampal NG2+ transcriptome with glucocorticoids being an important mediator of the LBN-induced molecular changes. LBN altered the NG2+ transcriptome and these transcriptional effects were correlated with glucocorticoids levels. The functional relevance of one LBN-induced candidate gene, Scn7a, could be confirmed by an increase in the density of voltage-gated sodium (Nav) channel activated currents in hippocampal NG2+ cells. Scn7a remained upregulated until adulthood in LBN animals, which displayed impaired cognitive performance. Considering that Nav channels are important for NG2+ cell-to-neuron communication, our findings provide novel insights into the disruption of this process in LBN mice.

Targeting the Stress System During Gestation: Is Early Handling a Protective Strategy for the Offspring?

The perinatal window is a critical developmental time when abnormal gestational stimuli may alter the development of the stress system that, in turn, influences behavioral and physiological responses in the newborns. Individual differences in stress reactivity are also determined by variations in maternal care, resulting from environmental manipulations. Despite glucocorticoids are the primary programming factor for the offspring’s stress response, therapeutic corticosteroids are commonly used during late gestation to prevent preterm negative outcomes, exposing the offspring to potentially aberrant stress reactivity later in life. Thus, in this study, we investigated the consequences of one daily s.c. injection of corticosterone (25 mg/kg), from gestational day (GD) 14–16, and its interaction with offspring early handling, consisting in a brief 15-min maternal separation until weaning, on: (i) maternal behavior; and (ii) behavioral reactivity, emotional state and depressive-like behavior in the adolescent offspring. Corticosterone plasma levels, under non-shock- and shock-induced conditions, were also assessed. Our results show that gestational exposure to corticosterone was associated with diminished maternal care, impaired behavioral reactivity, increased emotional state and depressive-like behavior in the offspring, associated with an aberrant corticosterone response. The early handling procedure, which resulted in increased maternal care, was able to counteract the detrimental effects induced by gestational corticosterone exposure both in the behavioral- and neurochemical parameters examined. These findings highlight the potentially detrimental consequences of targeting the stress system during pregnancy as a vulnerability factor for the occurrence of emotional and affective distress in the adolescent offspring. Maternal extra-care proves to be a protective strategy that confers resiliency and restores homeostasis.

Maternal Nutrition and Offspring Stress Response-Implications for Future Development of Non-Communicable Disease: A Perspective From India.

Psychological stress is recognized as a major modifiable risk factor for adult non-communicable disease (NCD) that includes depression, type 2 diabetes mellitus, and cardiovascular disease. Dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activity resulting in either exaggerated or blunted cortisol responses, and altered autonomic cardiovascular control have been thought to underlie this association. The developmental origins hypothesis proposes that impaired nutrition during fetal and early postnatal growth is associated with a higher NCD risk later in life. Maternal nutrients are vital for fetal growth and development, and both maternal undernutrition and over nutrition as in the case of gestational diabetes are associated with higher NCD risk markers in the offspring. Recent studies suggest that fetal exposure to maternal nutritional imbalances may permanently alter cortisol and cardio-sympathetic stress-responsiveness, which may link early life nutrition with adult disease risk. A few recent studies that examined the association between low birth weight as a marker of fetal undernutrition and stress response in humans showed that lower birth weight was associated with an altered HPA axis and cardiovascular sympathetic nervous system responses to stress in adults as well as in children. In addition, altered stress responses in relation to gestational diabetes have been noted. In this paper, we present available evidence from India for the association between maternal nutrition and offspring stress responsiveness against the backdrop of global evidence, and discuss its role in the escalating NCD rates in this population. We also discuss the scope for future studies in India and other transitioning countries.

Stress reactivity in preschool-aged children: Evaluation of a social stress paradigm and investigation of the impact of prenatal maternal stress

Prenatal maternal stress is an established risk factor for somatic and psychological health of the offspring. A dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in offspring has been suggested as an important mechanism. However, the impact of prenatal stress on stress reactivity in preschool-aged children is not yet well understood. This is partly due to the fact that for this age group there is no stress test as well established as for older children and adults.In the present work a previously published stress test (Kryski et al., 2011) was evaluated in a large sample of 45-month-old children (n = 339). Furthermore, the relation between measures of prenatal maternal stress and cortisol reactivity was investigated. Prenatal stress was defined as psychopathology (self-report available for n = 339; expert-rating available for a subsample of n = 246) and perceived stress (n = 244) during pregnancy.The stress paradigm elicited significant increases in salivary cortisol 30 and 40 min after the test, and 60.8% of the children were classified as responders. Lower cortisol levels after the stress test were observed in the group of children with prenatal stress defined as maternal psychopathology (both self-reported and expert-rated). Maternal perceived stress as a continuous measure was not significantly associated with cortisol levels. However, when comparing children in the highest quartile of maternal perceived stress to all other children, significantly lower cortisol values were observed in the prenatally stressed group.The present study confirms the paradigm by Kryski et al. as an effective stress test for preschool-aged children. Moreover, it provides further evidence that prenatal stress impacts HPA axis reactivity. Future studies should target the timing, nature, and intensity of prenatal stressors and their effect on the stress response in offspring at different developmental stages.

5.51 The Effects of Pubertal Development and Biological Sex on Maladaptive Stress Responses in Offspring Following Parental Cancer

Three million children in the United States have a parent diagnosed with cancer, which is a significant and stressful life event for offspring. Recent research suggests that early-life stress and trauma are associated with increased risk for developing psychopathology. Although the biological mechanisms through which chronic stress impacts psychopathology are not clear, studies have shown that hypothalamic-pituitary-adrenal (HPA)-axis dysregulation, inflammation, and modulatory variables, such as sex and pubertal development, all play important roles. This study’s objectives were as follows: 1) to examine the mechanistic impact of parental cancer diagnosis on the risk for depression and functional impairment in offspring; and 2) to investigate the role that biological sex and pubertal development have in moderating these relationships.

Antenatal depression programs cortisol stress reactivity in offspring through increased maternal inflammation and cortisol in pregnancy: The Psychiatry Research and Motherhood – Depression (PRAM-D) Study

IntroductionAntenatal depression is associated with a broad range of suboptimal outcomes in offspring, although the underlying mechanisms are not yet understood. Animal studies propose inflammation and glucocorticoids as mediators of the developmental programming effect of prenatal stress on offspring stress responses, but studies in humans are not yet at this stage. Indeed, to date no single study has examined the effects of a rigorously defined, clinically significant Major Depressive Disorder (MDD) in pregnancy on maternal antenatal inflammatory biomarkers and hypothalamic-pituitary (HPA) axis, as well as on offspring HPA axis, behavior and developmental outcomes in the first postnatal year. MethodsA prospective longitudinal design was used in 106 women (49 cases vs. 57 healthy controls) to study the effect of MDD in pregnancy and associated antenatal biology (inflammatory and cortisol biomarkers), on offspring stress response (cortisol response to immunization, at 8 weeks and 12 months), early neurobehavior (Neonatal Behavioral Assessment Scale, NBAS, at day 6), and cognitive, language and motor development (Bayley Scales of Infant and Toddler Development at 12 months). ResultsCompared with healthy controls, women with MDD in pregnancy had raised interleukin (IL) IL-6 (effect size (δ) = 0.53, p = 0.031), IL-10 (δ = 0.53, p = 0.043), tumor necrosis factor alpha (δ = 0.90, p = 0.003) and vascular endothelial growth factor (δ = 0.56, p = 0.008), together with raised diurnal cortisol secretion (δ = 0.89, p = 0.006), raised evening cortisol (δ = 0.64, p = 0.004), and blunted cortisol awakening response (δ = 0.70, p = 0.020), and an 8-day shorter length of gestation (δ = 0.70, p = 0.005). Furthermore, they had neonates with suboptimal neurobehavioral function in four out of five NBAS clusters measured (range of δ = 0.45–1.22 and p = 0.049–<0.001) and increased cortisol response to stress at one year of age (δ = 0.87, p < 0.001). Lastly, maternal inflammatory biomarkers and cortisol levels were correlated with infant stress response, suggesting a mechanistic link. ConclusionThis study confirms and extends the notion that depression in pregnancy is associated with altered offspring behavior and biological stress response, and demonstrates that changes in maternal antenatal stress-related biology are associated with these infant outcomes.

Evolutionary conserved neural signature of early life stress affects animal social competence.

In vertebrates, the early social environment can persistently influence behaviour and social competence later in life. However, the molecular mechanisms underlying variation in animal social competence are largely unknown. In rats, high-quality maternal care causes an upregulation of hippocampal glucocorticoid receptors (gr) and reduces offspring stress responsiveness. This identifies gr regulation as a candidate mechanism for maintaining variation in animal social competence. We tested this hypothesis in a highly social cichlid fish, Neolamprologus pulcher, reared with or without caring parents. We find that the molecular pathway translating early social experience into later-life alterations of the stress axis is homologous across vertebrates: fish reared with parents expressed the glucocorticoid receptor gr1 more in the telencephalon. Furthermore, expression levels of the transcription factor egr-1 (early growth response 1) were associated with gr1 expression in the telencephalon and hypothalamus. When blocking glucocorticoid receptors (GR) with an antagonist, mifepristone (RU486), parent-reared individuals showed more socially appropriate, submissive behaviour when intruding on a larger conspecific's territory. Remarkably, mifepristone-treated fish were less attacked by territory owners and had a higher likelihood of territory takeover. Our results indicate that early social-environment effects on stress axis programming are mediated by an evolutionary conserved molecular pathway, which is causally involved in environmentally induced variation of animal social competence.

SIRT1 reduction is associated with sex-specific dysregulation of renal lipid metabolism and stress responses in offspring by maternal high-fat diet

Rodent models of maternal obesity have been associated with kidney damage and dysfunction in offspring. However, the underlying mechanisms are yet to be elucidated. In this study, female rats were fed a high-fat diet (HFD) for 6 weeks prior to mating, throughout gestation and lactation; both male and female offspring were examined at weaning. Our results demonstrate that renal lipid deposition was increased in male offspring only, which is associated with reduced protein expression of Sirtuin (SIRT) 1, an essential regulator of lipid metabolism and stress response. Other components in its signalling network including phosphorylated 5′-AMP-activated protein kinase (pAMPKα), Forkhead box FOXO3a and Peroxisome proliferator-activated receptor (PPAR)γ coactivator 1-alpha (PGC-1α) were also downregulated. By contrast, in female offspring, renal fat/lipid distribution was unchanged in coupling with normal SIRT1 regulation. Specific autophagy and antioxidant markers were suppressed in both sexes. On the other hand, fibronectin and Collagen type IV protein expression was significantly higher in the offspring born HFD-fed dams, particularly in the males. Collectively, these findings suggest that maternal HFD consumption can induce sex-specific changes in offspring kidney lipid metabolism and stress responses at early ages, which may underpin the risk of kidney diseases later in life.

Effects of maternal cortisol treatment on offspring size, responses to stress, and anxiety-related behavior in wild largemouth bass (Micropterus salmoides)

Cortisol, the main glucocorticoid stress hormone in teleost fish, is of interest as a mediator of maternal stress on offspring characteristics because it plays an organizational role during early development. The present study tested the hypothesis that maternal exposure to cortisol treatment prior to spawn affects offspring phenotype using wild largemouth bass (Micropterus salmoides). Baseline and stress-induced cortisol concentrations, body size (i.e. length and mass), and behavior (i.e. anxiety, exploration, boldness, and aggression) were assessed at different offspring life-stages and compared between offspring of control and cortisol-treated females. Cortisol administration did not affect spawning success or timing, nor were whole-body cortisol concentrations different between embryos from cortisol-treated and control females. However, maternal cortisol treatment had significant effects on offspring stress responsiveness, mass, and behavior. Compared to offspring of control females, offspring of cortisol-treated females exhibited larger mass right after hatch, and young-of-the-year mounted an attenuated cortisol response to an acute stressor, and exhibited less thigmotaxic anxiety, exploratory behavior, boldness and aggression. Thus, offspring phenotype was affected by elevated maternal cortisol levels despite the absence of a significant increase in embryo cortisol concentrations, suggesting that a mechanism other than the direct deposition of cortisol into eggs mediates effects on offspring. The results of the present raise questions about the mechanisms through which maternal stress influences offspring behavior and physiology, as well as the impacts of such phenotypic changes on offspring fitness.