Effects Of Prenatal Stress Research Articles

Developmental stress has sex-specific effects on contextual and cued fear conditioning in adulthood

Stress-induced deviations in central nervous system development has long-term effects on adult mental health. Previous research in humans demonstrates that prenatal or adolescent stress increases the risk for psychiatric disorders. Animal models investigating the effects of stress during prenatal or adolescent development produces behavioral outcomes analogous to those observed in humans. However, whether adolescent stress exposure potentiates the effects of prenatal stress is currently unknown. Thus, the current study tested whether adolescent stress increases the impact of prenatal stress on contextual and cued fear memory in adulthood. Male and female Sprague Dawley rats were exposed to a chronic variable stress schedule during the last week of gestation, during adolescence, or during both developmental periods before undergoing fear conditioning training in adulthood. Our hypothesis predicted that the combined effects of prenatal and adolescent stress on contextual and cued fear memory would be greater than the effects of stress during either time period alone. In contrast to our hypothesis, however, we found independent effects of prenatal and adolescent stress on contextual and cued fear memory in both sexes, with no additional combined impact of stress exposure during both developmental phases. In males, developmental stress increased freezing behavior during contextual and cued testing regardless of whether stress exposure was prenatal, adolescent, or combined prenatal and adolescent stress exposure. In contrast, the effects of developmental stress in females were both test- and ovarian hormone status-dependent. During cued testing, nonstressed female freezing behavior depended on estrous cycle phase, whereas freezing behavior in stressed females did not, suggesting that developmental stress interferes with hormone-dependent cued fear memory. No effects of developmental stress or estrous cycle phase were observed for contextual fear memory in females. The results of the current study suggest that the effects of prenatal and adolescent stress on contextual and cued fear memory are not cumulative, but the effects of developmental stress on associative memory differ between males and females.

The effect of prenatal stress on antioxidant glutathion-assosiated enzymes activity in subcellular fractions of rat's liver

The activity of glutathione-associated antioxidant enzymes in subcellular fractions (cytosolic, mitochondrial, and cell nucleus fractions) was investigated in the liver of adult male Wistar rats born after prenatal stress was. Two groups of animals were studied in the experiment: (1) control group included - animals was born by intact mothers, and (2) prenatal stress group included animals whose mothers were subjected to immobilization stress in high-light conditions from the 15th to the 19th day of pregnancy. The activity of glutathione peroxidase (EC 1.11.1.9) in prenatally stressed animals decreased in the fractions of nuclei and mitochondria compared to the control group, while the activity of glutathione reductase (EC 1.8.1.7.) increased in the same subcellular fractions. The activity of glutathione transferase (EC 2.5.1.18) in prenatally stressed rats reduced in the cytosol and mitochondrial fractions as compared to control group. Redistribution of the antioxidant enzyme activity in the cytosol, the fraction of nuclei and the mitochondrial fraction of liver tissue may contribute to the formation of the pathological phenotype of prenatally stressed offspring.

Supplemental Material for In Vivo Microdialysis Shows Differential Effects of Prenatal Protein Malnutrition and Stress on Norepinephrine, Dopamine, and Serotonin Levels in Rat Orbital Frontal Cortex

Supplemental Material for In Vivo Microdialysis Shows Differential Effects of Prenatal Protein Malnutrition and Stress on Norepinephrine, Dopamine, and Serotonin Levels in Rat Orbital Frontal Cortex

Happiness in Pregnant African American Women: What Are the Biobehavioral Correlates?

The detrimental effects of prenatal stress on maternal-infant well-being have been well established and highlight increased concern for pregnant African American women. Research supports the notion that positive emotions may have a beneficial impact on the stress process and outcomes. However, the data have been largely restricted to non-African American pregnant women. This study's purpose was to examine potential relationships of both positive (happiness) and negative (stress, anxiety, and depressive symptoms) emotions and pro-inflammatory cytokines (interleukins-1β, -6, -8, -12, -17, tumor necrosis factor, and interferon-γ) in 72 pregnant African American women for a more complete picture of the stress process in this at-risk population. Results of this exploratory secondary data analysis show strong positive correlations between negative emotions and strong negative correlations between happiness and negative emotions. Interleukin-8 was positively correlated with negative emotions and negatively correlated with happiness. Results show mean ratings of negative emotions were higher than previously reported with more heterogeneous samples, while happiness ratings were in the moderate range. Findings suggest that pregnant African American women may experience higher stress and depressive symptoms than women in more heterogeneous samples. However, moderate levels of happiness might contribute to buffering the stress response.

Effects of prenatal stress on neuroactive steroid responses to acute stress in adult male and female rats.

Acute swim stress results in the robust production of several neuroactive steroids, which act as mediators of the stress response. These steroids include glucocorticoids, and positive GABAA receptor modulatory steroids such as allopregnanolone and tetrahydrocorticosterone (THDOC), which potentiate inhibitory GABA signalling, thereby playing a role in the negative control of the hypothalamic‐pituitary‐adrenal (HPA) axis. Prenatally stressed (PNS) offspring exhibit increased vulnerability to stress‐related disorders and frequently display exaggerated HPA axis responses to stressors during adulthood, which may be a result of reduced neuroactive steroid production and consequently inhibitory signalling. Here, we investigated whether exposure of rats to prenatal social stress from gestational day 16‐20 altered neuroactive steroid production under non‐stress conditions and in response to an acute stressor (swim stress) in adulthood. Using liquid chromatography‐mass spectrometry, nine neuroactive steroids were quantified (corticosterone, deoxycorticosterone [DOC], dihydrodeoxycorticosterone, THDOC, progesterone, dihydroprogesterone, allopregnanolone, pregnenolone, testosterone) in plasma and in five brain regions (frontal cortex, hypothalamus, amygdala, hippocampus, brainstem) of male and female control and PNS rats. There was no difference in the neuroactive steroid profile between control and PNS rats under basal conditions. The increase in circulating corticosterone induced by acute swim stress was similar in control and PNS offspring. However, greater stress‐induced corticosterone and DOC concentrations were observed in the brainstem of male PNS offspring, whereas DOC concentrations were lower in the hippocampus of PNS females compared to controls, following acute stress. Although PNS rats did not show deficits in allopregnanolone responses to acute stress, there were modest deficits in the production of THDOC in the brainstem, amygdala, and frontal cortex of PNS males and in the frontal cortex of PNS females. The data suggest that neuroactive steroid modulation of GABAergic signalling following stress exposure may be affected in a sex‐ and region‐specific manner in PNS offspring.

356 Microbial origins in the developmental programming of offspring health

Abstract Adverse parental lifetime experiences, such as stress and malnutrition, are implicated in the risk for offspring metabolic, cardiovascular, and neurodevelopmental disorders. In recent years, the maternal microbiome has emerged as an important factor that affects maternal health and infant development during pregnancy and beyond. Using mouse models of maternal stress experience during pregnancy, we examined the hypothesis that maternal stress experience alters the composition of the maternal microbiota and this altered community is transmitted to offspring to mediate effects of prenatal stress. As maternal stress exposure exhibits disruptive effects on both in utero environment and maternal microbiota, it has been difficult to assess the mechanistic involvement of the maternal microbiome to the prenatal stress phenotype independent of stress effects on the fetal environment. To circumvent this, we developed a maternal microbiota transplantation method in which embryonic day 18.5 mouse pups were delivered by caesarean section, thereby preventing natural colonization, and then transplanted with various maternal microbiota communities via orogastric gavage. Transplantation of maternal microbiota from stressed dams into naïve pups delivered by caesarean section recapitulated phenotypes that resembled those seen in prenatally stressed males, including reduced body weight and increased neuroendocrine response to acute stressors. However, transplantation of control maternal vaginal microbiota into prenatally stressed pups delivered by caesarean section did not rescue the prenatal stress phenotype. We showed that the inability to rescue the prenatal stress phenotype is related to transcriptional reprogramming to pathways involved in the regulation of innate immunity in the fetal gut and brain prior to birth and colonization by maternal microbiota. These results are interesting in light of recent studies demonstrating a critical role of the maternal microbiome on homeostasis of immune cell populations in the offspring brain. As an important requirement for normal growth and development, metabolites produced by the maternal gut microbiota cross the placental barrier and gain access to fetal circulation. Thus, we examined the hypothesis that maternal stress experience during pregnancy significantly alters the availability of maternal gut microbiota-derived metabolites, thereby shifting the availability of these metabolites required for the developing brain. Metabolomic profiling of the maternal compartment and fetal brain showed stress-induced reduction in a class of microbiota-derived metabolites involved in immune homeostasis and chromatin remodeling. Indeed, functional profiling of immune populations in the fetal brain revealed an association between reduced metabolite availability and increased infiltration of proinflammatory monocytes in the fetal brain. Further, as the gut microbiome is fairly accessible within clinical settings, we are now also asking how our mouse model translates to humans in a cohort of pregnant women exposed to childhood adversity. Collectively, our results suggest that intergenerational transmission of stress exposure occur via the maternal microbiota through two novel mechanisms. First, stress alterations during pregnancy impact the available pool of maternal gut microbiota-derived metabolites necessary for normal prenatal growth and development. Second, transmission of stress-altered vaginal microbiota may alter critical immune and metabolic processes underlying neurodevelopment.

86 Evaluation of the effect of prenatal transportation stress on endocrine and immune tissues of neonatal Brahman calves

Abstract The objective of this experiment was to evaluate whether prenatal transportation stress (PNS) affects the weight of endocrine and immune tissues of calves. Mature Brahman cows inseminated to a single Brahman sire in 2018 were assigned to be either Control (n = 35; not transported) or PNS (n = 37; 2 h of transportation at 60, 80, 100, 120, and 140 ± 5 d of gestation). Of the calves born in 2019, 16 Control (8 bulls and 8 heifers) and 16 PNS (8 bulls and 8 heifers) calves were studied. Pen score, body weight, and blood samples were obtained from calves at 25 ± 2 d of age. At that time, calves were euthanized by barbiturate overdose in order to collect tissues (brain, pituitary and adrenal glands, spleen and thymus). Tissues were trimmed and weighed. Serum cortisol was determined by RIA. Data were analyzed using ANOVA, GLM, and CORR procedures of SAS with body weight at sample collection as a covariate. Whole pituitary weight tended (P = 0.08) to be greater in females compared to males, whereas anterior pituitary weight tended (P = 0.06) to be greater in PNS. Whole brain weight was greater (P < 0.01) in males. The interaction of treatment and sex on whole brain weight of PNS tended (P = 0.09) to fall between that of the Control females and Control males. Whole pituitary weight was positively correlated with total adrenal weight (r = 0.32; P = 0.08). Total thymus weight positively correlated with whole brain and total adrenal weight (r = 0.43 and 0.41, respectively; P < 0.05). Serum cortisol was negatively correlated with spleen weight and total immune tissue weight (r = -0.37 and -0.38, respectively; P < 0.05). Results suggest next steps should include a closer look at function of immune tissues by studying PNS effect on thymus response to immunization.

Effects of prenatal stress on behavioural and neurodevelopmental outcomes are altered by maternal separation in the neonatal period

BackgroundChronic psychosocial stress during pregnancy and/or after birth, and the associated elevation in cortisol, is linked with the onset of behavioural disorders in childhood. Previously, prenatal stress has been shown to reduce neurosteroid pathways in the fetus and the levels of the neurosteroid and GABAA receptor agonist, allopregnanolone. In late gestation, elevated levels of GABAergic activity increases inhibitory tone and protects against excessive excitation. These levels of allopregnanolone may also contribute to promoting myelination, thus stress-induced suppression of protective neurosteroid levels may disrupt neurodevelopmental processes and can result in reduced myelination. The objective of this study was to examine whether prenatal and postnatal stress reduces levels of inhibitory pathways to result in behavioural, myelin, and GABAergic/glutamatergic pathway deficits in the hippocampus at a postnatal time point in the guinea pig equivalent to childhood in humans. MethodsPregnant guinea pig dams were exposed to prenatal stress (PRE) with strobe light exposure for 2 h/day on gestational age (GA) 50, 55, 60 and 65 (term is ∼GA70), with postnatal stress (POST) caused by maternal separation for 2 h/day from postnatal day (PND) 1–7), or a double-hit of both stressors (PRE + POST). Control dams and offspring groups (CON) were handled at the same time each day without causing stress. Behavioural outcomes were assessed using open field and elevated plus maze testing on PND27. After euthanasia on PND30, plasma samples were collected for steroid quantification of cortisol, allopregnanolone and progesterone by ELISA. Hippocampal samples were collected to assess markers of oligodendrocyte development and mature cells by myelin basic protein (MBP) immunostaining and GABAergic and glutamatergic pathway component gene expression by real time PCR. ResultsMale guinea pig offspring exposed to prenatal stress exhibited hyperactive-like behaviour at childhood equivalence, while female offspring displayed anxious-like behaviour, to a lesser extent. In both sexes, MBP immunostaining was significantly decreased in the hippocampal region following prenatal stress, despite normal levels of MBP mRNA, which suggests a disruption to the MBP protein translation pathway. Many components of the GABAergic and glutamatergic pathways were disrupted following prenatal stress, notably GABAA receptor subunits, GABA production and uptake, glutamate ionotropic and metabotropic receptor subunits and glutamate transport. Following prenatal + postnatal stress, many of the behavioural and neurodevelopmental deficits were improved compared to the prenatal stress only group. ConclusionWe conclude that prenatal stress disrupts GABAergic and glutamatergic pathways that may contribute to reduced myelination and subsequent behavioural deficits in the offspring. The deficits seen following prenatal stress are ameliorated when paired with subsequent postnatal stress, which highlights the early postnatal period as an important treatment window.

Moving the dial on prenatal stress mechanisms of neurodevelopmental vulnerability to mental health problems: A personalized prevention proof of concept.

Prenatal stress exposure increases vulnerability to virtually all forms of psychopathology. Based on this robust evidence base, we propose a "Mental Health, Earlier" paradigm shift for prenatal stress research, which moves from the documentation of stress-related outcomes to their prevention, with a focus on infant neurodevelopmental indicators of vulnerability to subsequent mental health problems. Achieving this requires an expansive team science approach. As an exemplar, we introduce the Promoting Healthy Brain Project (PHBP), a randomized trial testing the impact of the Wellness-4-2 personalized prenatal stress-reduction intervention on stress-related alterations in infant neurodevelopmental trajectories in the first year of life. Wellness-4-2 utilizes bio-integrated stress monitoring for just-in-time adaptive intervention. We highlight unique challenges and opportunities this novel team science approach presents in synergizing expertise across predictive analytics, bioengineering, health information technology, prevention science, maternal-fetal medicine, neonatology, pediatrics, and neurodevelopmental science. We discuss how innovations across many areas of study facilitate this personalized preventive approach, using developmentally sensitive brain and behavioral methods to investigate whether altering children's adverse gestational exposures, i.e., maternal stress in the womb, can improve their mental health outlooks. In so doing, we seek to propel developmental SEED research towards preventive applications with the potential to reduce the pernicious effect of prenatal stress on neurodevelopment, mental health, and wellbeing.

Maternal antioxidant treatment prevents the adverse effects of prenatal stress on the offspring's brain and behavior

Maternal exposure to stress during pregnancy is associated with an increased risk of psychiatric disorders in the offspring in later life. The mechanisms through which the effects of maternal stress are transmitted to the fetus are unclear, however the placenta, as the interface between mother and fetus, is likely to play a key role. Using a rat model, we investigated a role for placental oxidative stress in conveying the effects of maternal social stress to the fetus and the potential for treatment using a nanoparticle-bound antioxidant to prevent adverse outcomes in the offspring.Maternal psychosocial stress increased circulating corticosterone in the mother, but not in the fetuses. Maternal stress also induced oxidative stress in the placenta, but not in the fetal brain. Blocking oxidative stress using an antioxidant prevented the prenatal stress-induced anxiety phenotype in the male offspring, and prevented sex-specific neurobiological changes, specifically a reduction in dendrite lengths in the hippocampus, as well as reductions in the number of parvalbumin-positive neurons and GABA receptor subunits in the hippocampus and basolateral amygdala of the male offspring. Importantly, many of these effects were mimicked in neuronal cultures by application of placental-conditioned medium or fetal plasma from stressed pregnancies, indicating molecules released from the placenta may mediate the effects of prenatal stress on the fetal brain. Indeed, both placenta-conditioned medium and fetal plasma contained differentially abundant microRNAs following maternal stress, and their predicted targets were enriched for genes relevant to nervous system development and psychiatric disorders.The results highlight placental oxidative stress as a key mediator in transmitting the maternal social stress effects on the offspring's brain and behavior, and offer a potential intervention to prevent stress-induced fetal programming of affective disorders.

Long-term effects of stress early in life on microRNA-30a and its network: Preventive effects of lurasidone and potential implications for depression vulnerability

Exposure to early life stress can interfere with neurodevelopmental trajectories to increase the vulnerability for psychiatric disorders later in life. With this respect, epigenetic mechanisms play a key role for the long-lasting changes in brain functions that may elicit and sustain psychopathologic outcomes.Here, we investigated DNA methylation changes as possible epigenetic mechanism mediating the effect of prenatal stress (PNS), an experimental paradigm associated with behavioral and molecular alterations relevant for psychiatric disorders. We identified 138 genes as being differentially methylated in the prefrontal cortex (PFC) and in the hippocampus (HIP) of male and female adult rats exposed to PNS. Among these genes, miR-30a and Neurod1 emerged as potential players for the negative outcomes associated with PNS exposure. Indeed, in addition to showing consistent methylation differences in both brain regions and in both sexes, and interacting with each other, they are both involved in Axon guidance and Neurotrophin signaling, which are important to neurodevelopmental disorders. We also found a significant reduction in the expression of a panel of genes (CAMK2A, c-JUN, LIMK1, MAP2K1, MAP2K2, PIK3CA and PLCG1) that belong to these two biological pathways and are also validated targets of miR-30a, pointing to a down-regulation of these pathways as a consequence of PNS exposure. Interestingly, we also found that miR-30a levels were significantly upregulated in depressed patients exposed to childhood trauma, as compared to control individuals. Importantly, we also found that a sub-chronic treatment with the atypical antipsychotic drug, lurasidone, during adolescence was able to prevent the up-regulation of miR-30a and normalized the expression of its target genes in response to PNS exposure.Our results demonstrate that miR-30a undergoes epigenetic changes following early life stress exposure and suggest that this miRNA could play a key role in producing broad and long-lasting alterations in neuroplasticity-related pathways, contributing to the etiology of psychiatric disorders.

Sex differences in the neurochemistry of frontal cortex: Impact of early life stress.

Traumatic events during early life have been linked with later life psychopathology. To understand this risk factor, researchers have studied the effects of prenatal and postnatal early life stress on neurochemical changes. Here we review the rodent literature on sex differences and sex-specific impact of early life stress on frontal cortex neurochemistry. This region is implicated in regulating motivation and emotion, which are often disrupted in psychological disorders. The prefrontal cortex (PFC) in particular is one of the last brain regions to develop, and there are sex differences in the rate of this development. To draw direct comparisons between sexes, our review of the literature was restricted to studies where the effects of prenatal or postnatal stress had been described in male and female littermates. This literature included research describing glutamate, γ-amino butyric acid (GABA), corticosteroids, monoamines, and cannabinoids. We found that sex-dependent effects of stress are mediated by the age at which stress is experienced, age at test, and type of stress endured. More research is required, particularly into the effects of adolescent stress on male and female littermates. We hope that a greater understanding of sex-specific susceptibilities in response to stress across development will help to uncover risk factors for psychological disorders in vulnerable populations.

Combination of Stressors in the Critical Periods of Development Increases Resistance to Inflammatory Pain Stress in Adult Rats

We report here studies of the long-term effects of combined stress in the prenatal and prepubertal periods of development on measures of tonic inflammatory pain in the formalin test and the severity of depression-like behavior, and also the stress reactivity of the hormonal response in adult rats. In addition, the effects of the serotonin (5-HT) reuptake inhibitor fluoxetine and the 5-HT1A receptor agonist buspirone, given chronically to stressed mothers during pregnancy, on various types of adaptive behavior impaired by prenatal stress were assessed in rats of both sexes. The results showed that in rats of both sexes prenatal stress increased the pain response organized at the spinal and supraspinal levels of the central nervous system and that fluoxetine and buspirone normalized responses. Stress during the prepuberal period of development eliminated the effects of prenatal stress on the inflammatory pain responses integrated at the supraspinal level in adult rats; in these conditions, fluoxetine and buspirone had no effects, in contrast to their antinociceptive actions on the pain response integrated at the spinal level. Stress at prepubertal age eliminated sex-related differences seen in depression-like behavior in prenatally unstressed and prenatally stressed rats given physiological saline. Control adult females and adult females exposed to prenatal stress in the prepubertal period showed increases in the plasma corticosterone level after forced swimming as compared with the basal hormone level, though there were no significant differences in the level of stress reactivity of the hormonal response after forced swimming. Thus, the conditions for stress actions increasing stress resistance in adult rats were identified. Stress in the critical period of development formed a phenotype with increased stress resistance to inflammatory pain, which was seen in responses organized at the supraspinal level in adult individuals.

Prenatal stress-related alterations in synaptic transmission and 5-HT7 receptor-mediated effects in the rat dorsal raphe nucleus are ameliorated by the 5-HT7 receptor antagonist SB 269970.

Early life adversity exerts a detrimental influence on developing brain neuronal networks and its consequences may include mental health disorders. In rats, prenatal stress may lead to anxiety and depressive-like behavior in the offspring. Several lines of evidence implicated an involvement of prenatal stress in alterations of the brain serotonergic system functions, but the effects of prenatal stress on its core, the dorsal raphe nucleus (DRN), still remain incompletely understood. The present study was aimed at finding whether prenatal stress induces modifications in the glutamatergic and GABAergic inputs to DRN projection cells and whether it affects DRN 5-HT7 receptors, which modulate activity of these synapses. Prenatal stress resulted in an increase in basal frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and in a decrease in basal frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded from putative projection neurons in DRN slices ex vivo. While there were no changes in the excitability of DRN projection neurons, the 5-HT7 receptor-mediated reduction in the sEPSC frequency and rise in the sIPSC frequency, seen in control rats, were largely absent in slices obtained from prenatally stressed rats. Repeated administration of SB 269970, a 5-HT7 receptor antagonist, resulted in a reversal of prenatal stress-induced alterations in 5-HT7 receptor-mediated effects on the sEPSC/sIPSC frequency. Moreover, the treatment reversed prenatal stress-induced alterations in basal excitatory transmission and partially reversed the effect of stress on basal inhibitory transmission in the DRN.

Resolving Late Consequences of Prenatal Stress with Dynamic Tandem Hypnotherapy (DTH)

Dynamic Tandem Hypnotherapy (DTH) was evolved more than ten years ago by the authors. It designates a kind of group-hypnotherapy, which is used for resolving late pathological consequences of prenatal traumas. In tandem hypnotherapy sessions more than two persons take part in: the patient and the co-therapist, who touch each other and go into a trance together; while the hypnotherapist keeps the distance. A mutual attunement is developed between the participants being in a tandem trance, which seems as serving for the therapeutic effect. Touch is considered as having the possibility to create calm, safety, and love, which are viewed to be lost or confined by unbearable emotions of prenatal traumas. Moreover, touch is viewed as the mother of perceptions, the ‟skin-ego,” which already functions when there is no central nervous system developed yet. Thus consequences of prenatal stress can be healed with such a therapeutic approach at the same functional level on which the trauma occurred. Four case vignettes will be shown with interpretations upon how DTH works.

Maternal prenatal depression and epigenetic age deceleration: testing potentially confounding effects of prenatal stress and SSRI use

ABSTRACT Previous studies suggest epigenetic alterations may contribute to the association between maternal prenatal depression and adverse offspring outcomes. Developmental researchers have recently begun to examine these associations in relation to epigenetic age acceleration/deceleration, a biomarker of developmental risk that reflects the deviation between epigenetic age and chronological age. In the perinatal period, preliminary studies indicate that maternal prenatal depression may lead to epigenetic age deceleration in newborns, which may predict adverse developmental outcomes. The present study examined the relationship between maternal prenatal exposures (i.e., depression, stress, and SSRI use) and offspring epigenetic age deceleration in 303 mother-offspring dyads. Women were recruited in the first trimester of pregnancy and followed longitudinally until delivery. Maternal depression, perceived stress, and SSRI use were assessed at each prenatal visit. Newborn epigenetic age was determined via cord blood samples. Results indicated maternal prenatal stress was not associated with newborn epigenetic age deceleration (ΔR2 = 0.002; p = 0.37). Maternal prenatal depression was associated with decelerated epigenetic age (ΔR2 = 0.01, p = 0.04), but this relationship did not hold when accounting for maternal use of SSRIs (ΔR2 = 0.002, p = 0.43). Conversely, maternal SSRI use significantly predicted newborn epigenetic age deceleration over and above the influence of maternal depression (ΔR2 = 0.03, p = 0.001). These findings suggest maternal prenatal SSRI use may significantly contribute to the previously documented association between maternal prenatal depression and epigenetic age deceleration. Further studies are needed to examine how these epigenetic differences at birth may contribute to adverse outcomes in later development.

Childhood Anxiety: Prenatal Maternal Stress and Parenting in the QF2011 Cohort.

In this study we examine whether specific 'anxiety-maintaining' parenting behaviors (i.e., overinvolvement and/or negativity) exacerbate the effects of disaster-related prenatal maternal stress (PNMS) on school-age anxiety symptoms. Women (N = 230), pregnant at the time of the 2011 Queensland Floods, reported on their experience of flood-related PNMS (objective hardship, cognitive appraisal, subjective distress). At 4-years, mother-child dyads were coded for maternal overinvolvement and negativity during a challenging task; at 6-years mothers reported on their children's anxiety symptoms and their own mood, N = 83. Results showed no associations between PNMS and 6-year anxiety, nor did parenting moderate these effects. Poorer maternal concurrent mood was associated with greater anxiety symptoms at 6years (β = 0.52). Findings suggest maternal concurrent mood, but not exposure to disaster-related PNMS nor 'anxiety-maintaining' parenting behaviors at preschool age, is related to school-age anxiety symptoms.

Effects of Prenatal Stress on the Formation of the Orexinergic System of the Hypothalamus in Rats

The effects of prenatal stress (PNS) on the formation of the orexinergic and dopaminergic systems of the brain were studied in 14- and 30-day-old rat pups born to females subjected to sleep deprivation (6 h/day) using the “small areas” method from day 13 to day 19 of pregnancy. The open fi eld test showed impairments to motor development in 14-day-old PNS rat pups. Immunohistochemical studies of brain sections showed that the hypothalamus contained a signifi cantly larger quantity of orexin A in neurons in the periforniceal area, while high-performance liquid chromatography demonstrated increases in the dopamine level and its rate of metabolism as compared with control rat pups born to intact females. Western blotting results provided evidence of a decrease in the striatal level of the GABA-sythesizing enzyme (GAD65) and an increase in the level of tyrosine hydroxylase (an enzyme involved in dopamine synthesis) phosphorylated at serine-40 as compared with controls. By day 30 of life measures of motor activity in PNS rat pups were no different from those in controls, though PNS rat pups had higher levels of anxiety and lower levels of exploratory activity. The results of morphological and biochemical studies also provided evidence that there were no differences between the study parameters in the hypothalamus and striatum in 30-day-old rat pups as compared with controls, which was confi rmed by results from electrophysiological studies indicating that there were no differences in the organization of the sleep-waking cycle in 30-day-old PNS and control rat pups. We discuss here the morphofunctional interactions of the orexinergic and dopaminergic systems of the brain in the early postnatal period of development of the body and the role of orexins in the compensatory mechanisms of the brain.

Effect of prenatal transportation stress on DNA methylation in Brahman heifers

Prenatal stress in beef cattle has the potential to result in unexpected, long-term phenotypic changes to an animal's performance. One possible explanation for this phenomenon is stress-induced epigenetic alterations of the genome (e.g., methylation or histone modifications). The objective of this experiment was to identify differential DNA methylation patterns in prenatally stressed (PNS) Brahman females compared to control animals. Pregnant Brahman cows (n = 48) were transported for 2-h periods at 60 ± 5, 80 ± 5, 100 ± 5, 120 ± 5, and 140 ± 5 d. A non-transported group (n = 48) was maintained as a control (Control). Methylation of leukocyte DNA from 28-d old heifer calves born following the PNS exposure (Control n = 8, PNS n = 6) was assessed by reduced representation sodium bisulfite sequencing. Mean methylation ratios at locations across the genome in PNS and Control females were compared using Fisher's Exact t-tests. There were 16,377 CG sites, 309 CHG, and 612 CHH (C= cytosine; G= guanine; H = adenine, cytosine or thymine) sites that were differentially methylated in PNS females compared to the Control (P ≤ 0.05). Differentially methylated regions located in promoters of genes were analyzed to identify genetic pathways and biological functions potentially influenced by the alterations. Important pathways (P ≤ 0.05) included those involved in cell signaling, neurological development, cellular development, immune response, and metabolism. Alterations in expression of genes in pathways such as the “Axonal Guidance Signaling”, “Corticotrophin Releasing Hormone Signaling” and the Neurotrophin/TRK Signaling” pathways could change animal phenotypes.

Sex-dependent metabolic effects of pregestational exercise on prenatally stressed mice.

Stressful events during the prenatal period have been related to hyperactive hypothalamic-pituitary-adrenal (HPA) axis responses as well as metabolic changes in adult life. Moreover, regular exercise may contribute to the improvement of the symptoms associated with stress and stress-related chronic diseases. Therefore, this study aims to investigate the effects of exercise, before the gestation period, on the metabolic changes induced by prenatal stress in adult mice. Female Balb/c mice were divided into three groups: control (CON), prenatal restraint stress (PNS) and exercise before the gestational period plus PNS (EX+PNS). When adults, the plasmatic biochemical analysis, oxidative stress, gene expression of metabolic-related receptors and sex differences were assessed in the offspring. Prenatal stress decreased neonatal and adult body weight when compared to the pregestational exercise group. Moreover, prenatal stress was associated with reduced body weight in adult males. PNS and EX+PNS females showed decreased hepatic catalase. Pregestational exercise prevented the stress-induced cholesterol increase in females but did not prevent the liver mRNA expression reduction on the peroxisome proliferator-activated receptors (PPARs) α and γ in PNS females. Conversely, PNS and EX+PNS males showed an increased PPARα mRNA expression. In conclusion, pregestational exercise prevented some effects of prenatal stress on metabolic markers in a sex-specific manner.