scholarly journals Effects of maternal exposure to social stress during pregnancy: consequences for mother and offspring

Reproduction ◽  
2013 ◽  
Vol 146 (5) ◽  
pp. R175-R189 ◽  
Author(s):  
Paula J Brunton
Keyword(s):  
Hpa Axis ◽  
Prenatal Stress ◽  
Social Stress ◽  
Maternal Stress ◽  
Reproductive Potential ◽  
Maternal Behaviour ◽  
Stress Exposure ◽  
Prenatally Stressed ◽  
In Pregnancy

A suboptimalin uteroenvironment, for example, as a result of maternal stress, can have detrimental effects on the pregnancy and long-term adverse ‘programming’ effects on the offspring. This article focuses on the effects of prenatal social stress on the mother, her pregnancy and the offspring, since these issues have ethological relevance in both animals and humans. The consequences of social stress exposure depend on when during pregnancy the stress occurs, and many of the effects on the offspring are sex specific. Social stress during early pregnancy tends to result in pregnancy loss, whereas stress exposure later in pregnancy, when the mother has already invested considerable resources in the foetuses, results in programmed offspring of low birth weight: a risk factor for various adulthood diseases. Neuroendocrine and behavioural responses to stress in the offspring are particularly sensitive to foetal programming by prenatal stress, indicated by enhanced hypothalamo-pituitary–adrenal (HPA) axis responses and increased anxiety behaviour, which result from permanent changes in the offspring's brain. The dysregulation of HPA axis function may also interfere with other systems, for example, the hypothalamic–pituitary–gonadal axis, as there is evidence for alterations in steroidogenesis, reproductive potential and impaired reproductive/social behaviours in prenatally stressed offspring. Prenatal social stress also programmes future maternal behaviour, highlighting the potential for negative phenotypes to be transmitted to future generations. The possible mechanisms through which maternal stress during pregnancy is transmitted to the foetuses and the foetal brain is programmed by prenatal stress and the potential to overwrite programming of the offspring are discussed.

scholarly journals 356 Microbial origins in the developmental programming of offspring health

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 93-94
Author(s):  
Eldin Jašarević
Keyword(s):  
Caesarean Section ◽  
Gut Microbiota ◽  
Prenatal Stress ◽  
Growth And Development ◽  
Maternal Stress ◽  
Fetal Brain ◽  
Vaginal Microbiota ◽  
Stress Exposure ◽  
Prenatally Stressed ◽  
Stress Experience

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.

scholarly journals Maternal antioxidant treatment prevents behavioural and neural changes in offspring exposed to prenatal social stress

2019 ◽  
Author(s):  
H Scott ◽  
TJ Phillips ◽  
Y Sze ◽  
A Alfieri ◽  
MF Rogers ◽  
...  
Keyword(s):  
Conditioned Medium ◽  
Prenatal Stress ◽  
Social Stress ◽  
Maternal Stress ◽  
Later Life ◽  
Neuronal Cultures ◽  
Antioxidant Treatment ◽  
Foetal Brain ◽  
Increased Risk

AbstractMaternal exposure to social stress during pregnancy is associated with an increased risk of psychiatric disorders in the offspring in later life. However, the mechanism through which the effects of maternal stress are transmitted to the foetus is unclear. Using a rat model, we explored the mechanisms by which maternal social stress is conveyed to the foetus and the potential for targeted treatment to prevent disease in the offspring. Maternal stress increased circulating corticosterone in the mother, but not the foetuses. Maternal stress also induced oxidative stress in the placenta, but not in the foetal brain, and this was prevented by administration of a nanoparticle-bound antioxidant. Moreover, antioxidant treatment prevented prenatal stress-induced anxiety-like behaviour in the adult male offspring, along with several stress-induced neuroanatomical, neurochemical and gene expression changes in the offspring brain. Importantly, many of these neural effects were mimicked in neuronal cultures by application of placental-conditioned medium or foetal plasma from stressed pregnancies. Both placental-conditioned medium and foetal plasma contained differentially abundant extracellular microRNAs following prenatal stress. The present study highlights the crucial role of the placenta, and the molecules it secretes, in foetal brain development and provides evidence of the potential for treatment that can prevent maternal stress-induced foetal programming of neurological disease.

Maternal stress does not exacerbate long-term bone deficits in female rats born growth restricted, with differential effects on offspring bone health

2018 ◽  
Vol 314 (2) ◽  
pp. R161-R170 ◽  
Author(s):  
Kristina Anevska ◽  
Jean N. Cheong ◽  
John D. Wark ◽  
Mary E. Wlodek ◽  
Tania Romano
Keyword(s):  
Bone Health ◽  
Bending Strength ◽  
Maternal Stress ◽  
Quantitative Computed Tomography ◽  
Peripheral Quantitative Computed Tomography ◽  
Female Offspring ◽  
Female Rats ◽  
Stress Exposure ◽  
Wistar Kyoto

Females born growth restricted have poor adult bone health. Stress exposure during pregnancy increases risk of pregnancy complications. We determined whether maternal stress exposure in growth-restricted females exacerbates long-term maternal and offspring bone phenotypes. On gestational day 18, bilateral uterine vessel ligation (restricted) or sham (control) surgery was performed on Wistar-Kyoto rats. At 4 mo, control and restricted females were mated and allocated to unstressed or stressed pregnancies. Stressed pregnancies had physiological measurements performed; unstressed females were not handled. After birth, mothers were aged to 13 mo. Second-generation (F2) offspring generated four experimental groups: control unstressed, restricted unstressed, control stressed and restricted stressed. F2 offspring were studied at postnatal day 35 (PN35), 6, 12, and 16 mo. Peripheral quantitative computed tomography was performed on maternal and F2 offspring femurs. Restricted females, irrespective of stress during pregnancy, had decreased endosteal circumference, bending strength, and increased osteocalcin concentrations after pregnancy at 13 mo. F2 offspring of stressed mothers were born lighter. F2 male offspring from stressed pregnancies had decreased trabecular content at 6 mo and decreased endosteal circumference at 16 mo. F2 female offspring from growth-restricted mothers had reduced cortical thickness at PN35 and reduced endosteal circumference at 6 mo. At 12 mo, females from unstressed restricted and stressed control mothers had decreased trabecular content. Low birth weight females had long-term bone changes, highlighting programming effects on bone health. Stress during pregnancy did not exacerbate these programmed effects. Male and female offspring responded differently to maternal growth restriction and stress, indicating gender-specific programming effects.

scholarly journals Early and long-term neuroendocrine effects of prenatal stress in male and female rats

2000 ◽  
Vol 46 (1) ◽  
pp. 30-34 ◽  
Author(s):  
A. G. Reznikov ◽  
N. D. Nosenko ◽  
L. V. Tarasenko ◽  
P. V. Sinitsyn ◽  
L. I. Polyakova
Keyword(s):  
Prenatal Stress ◽  
Stress Reactivity ◽  
Female Rats ◽  
Male And Female Rats ◽  
Prenatally Stressed ◽  
Old Rats ◽  
Males And Females ◽  
Morphological Equivalent ◽  
The Brain

The effect of maternal stress or so-called prenatal stress (PS) on the neuroendocrine regulation of reproduction and stress reactivity of the progeny was studied. Prenatal stress prevented the formation of sex dimorphism of catecholamine content and aromatase and androgen 5a-reductase activities in the preoptic region of the brain and mediobasal hypothalamus of 10-day-old rats. Leveling of sex-specific differences in the size of the neurocyte nuclei in the suprachiasmatic nucleus was the morphological equivalent of functional disorders induced by PS. Stress and adrenergic reactivity of the hypothalamo-pituitary-adrenal system was changed in prenatally stressed males and females. Remote effects of PS are regarded as a manifestation of disorders in the hormone neurotransmitter imprinting of the neuroendocrine system.

Effects of tail docking and castration on stress responses in lambs and the influence of prenatal glucocorticoid treatment

2013 ◽  
Vol 25 (7) ◽  
pp. 1020 ◽  
Author(s):  
Shaofu Li ◽  
Ilias Nitsos ◽  
Graeme R. Polglase ◽  
John P. Newnham ◽  
John R. G. Challis ◽  
...  
Keyword(s):  
Prenatal Exposure ◽  
Hpa Axis ◽  
Stress Responses ◽  
Plasma Cortisol ◽  
Female Offspring ◽  
Cortisol Response ◽  
Glucocorticoid Treatment ◽  
Tail Docking ◽  
In Pregnancy

It is common practice in Australian agriculture to remove the tails of lambs to prevent infection and to castrate males to prevent behavioural problems and unwanted reproduction. We have studied the pain and stress responses to these interventions by measuring changes in the hypothalamic–pituitary–adrenal (HPA) axis and β-endorphin levels. Further, we have evaluated the effects of prenatal exposure to dexamethasone, which is known to affect the developing HPA axis. In control animals that had received prenatal saline treatment, plasma cortisol and adrenocorticotrophin (ACTH) levels increased after the interventions in both females and males. Plasma β-endorphin levels also increased after the interventions, but the responses were less consistent. Prenatal dexamethasone exposure early in pregnancy (dexamethasone 0.14 mg kg–1 ewe weight injection commenced on day 40 of pregnancy for four consecutive intramuscular injections at 12-hourly intervals) blunted the cortisol response to tail docking in female offspring, but not to combined tail docking and castration in males. It had no effect on ACTH or β-endorphin responses in either sex. These findings describe the stress responses to these common agricultural interventions and suggest that long-term development of the HPA axis in females is altered by prenatal exposure to dexamethasone.

scholarly journals Epigenetic mechanisms in the development of behavior: Advances, challenges, and future promises of a new field

2013 ◽  
Vol 25 (4pt2) ◽  
pp. 1279-1291 ◽  
Author(s):  
Tania L. Roth
Keyword(s):  
Dna Methylation ◽  
Social Stress ◽  
Treatment Strategies ◽  
Traumatic Experiences ◽  
Future Research ◽  
Epigenetic Alterations ◽  
Stress Exposure ◽  
The Past ◽  
Gene Environment

AbstractIn the past decade, there have been exciting advances in the field of behavioral epigenetics that have provided new insights into a biological basis of neural and behavioral effects of gene–environment interactions. It is now understood that changes in the activity of genes established through epigenetic alterations occur as a consequence of exposure to environmental adversity, social stress, and traumatic experiences. DNA methylation in particular has thus emerged as a leading candidate biological pathway linking gene–environment interactions to long-term and even multigenerational trajectories in behavioral development, including the vulnerability and resilience to psychopathology. This paper discusses what we have learned from research using animal models and from studies in which the translation of these findings has been made to humans. Studies concerning the significance of DNA methylation alterations in outcomes associated with stress exposure later in life and dysfunction in the form of neuropsychiatric disorders are highlighted, and several avenues of future research are suggested that promise to advance our understanding of epigenetics both as a mechanism by which the environment can contribute to the development of psychiatric disorders and as an avenue for more effective intervention and treatment strategies.

scholarly journals Life stress and cortisol reactivity: An exploratory analysis of the effects of stress exposure across life on HPA-axis functioning

2020 ◽  
pp. 1-12 ◽  
Author(s):  
Ethan S. Young ◽  
Jenalee R. Doom ◽  
Allison K. Farrell ◽  
Elizabeth A. Carlson ◽  
Michelle M. Englund ◽  
...  
Keyword(s):  
Early Childhood ◽  
Hpa Axis ◽  
Life Stress ◽  
Social Stress ◽  
Acute Stress ◽  
Stress Test ◽  
Trier Social Stress Test ◽  
Stress Exposure ◽  
Cortisol Reactivity ◽  
Biological Stress

Abstract Stressful experiences affect biological stress systems, such as the hypothalamic–pituitary–adrenal (HPA) axis. Life stress can potentially alter regulation of the HPA axis and has been associated with poorer physical and mental health. Little, however, is known about the relative influence of stressors that are encountered at different developmental periods on acute stress reactions in adulthood. In this study, we explored three models of the influence of stress exposure on cortisol reactivity to a modified version of the Trier Social Stress Test (TSST) by leveraging 37 years of longitudinal data in a high-risk birth cohort (N = 112). The cumulative stress model suggests that accumulated stress across the lifespan leads to dysregulated reactivity, whereas the biological embedding model implicates early childhood as a critical period. The sensitization model assumes that dysregulation should only occur when stress is high in both early childhood and concurrently. All of the models predicted altered reactivity, but do not anticipate its exact form. We found support for both cumulative and biological embedding effects. However, when pitted against each other, early life stress predicted more blunted cortisol responses at age 37 over and above cumulative life stress. Additional analyses revealed that stress exposure in middle childhood also predicted more blunted cortisol reactivity.

scholarly journals Trans-generational effects of prenatal stress in quail

2013 ◽  
Vol 280 (1753) ◽  
pp. 20122368 ◽  
Author(s):  
Floriane Guibert ◽  
Sophie Lumineau ◽  
Kurt Kotrschal ◽  
Erich Möstl ◽  
Marie-Annick Richard-Yris ◽  
...  
Keyword(s):  
Prenatal Stress ◽  
Phenotypic Variability ◽  
Reproductive Traits ◽  
Long Term Effects ◽  
Stress Effects ◽  
Generational Transmission ◽  
Generational Effects ◽  
Prenatally Stressed ◽  
Yolk Testosterone

The prenatal environment is a source of phenotypic variability influencing the animal's characteristics. Prenatal stress affects not only the development of offspring, but also that of the following generation. Such effects have been best documented in mammals but can also be observed in birds, suggesting common processes across phylogenetic orders. We found previously that Japanese quail females stressed during laying produced offspring with higher fearfulness, probably related to modulation of testosterone levels in their eggs. Here, we evaluated long-term effects of prenatal stress by analysing reproductive traits of these F 1 offspring and, then, the development of their subsequent (F 2 ) offspring. The sexual behaviour of F 1 prenatally stressed (F1PS) males was impaired. F1PS females' eggs contained less yolk and more albumen, and higher yolk testosterone and progesterone levels than did F 1 prenatal control females. The fearfulness of F 2 prenatally stressed quail was greater than that of F 2 prenatal control quail. These F 2 behavioural differences paralleled those evidenced by their parents, suggesting trans-generational transmission of prenatal stress effects, probably mediated by egg compositions of F1PS females.

scholarly journals Gender differences in the long-term effects of chronic prenatal stress on the HPA axis and hypothalamic structure in rats

2010 ◽  
Vol 35 (10) ◽  
pp. 1525-1535 ◽  
Author(s):  
Cristina García-Cáceres ◽  
Natalia Lagunas ◽  
Isabel Calmarza-Font ◽  
Iñigo Azcoitia ◽  
Yolanda Diz-Chaves ◽  
...  
Keyword(s):  
Gender Differences ◽  
Hpa Axis ◽  
Prenatal Stress ◽  
Long Term Effects ◽  
Hypothalamic Structure

scholarly journals Sex-specific effects of prenatal stress on glucose homoeostasis and peripheral metabolism in rats

2013 ◽  
Vol 217 (2) ◽  
pp. 161-173 ◽  
Author(s):  
Paula J Brunton ◽  
Katie M Sullivan ◽  
David Kerrigan ◽  
John A Russell ◽  
Jonathan R Seckl ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Prenatal Stress ◽  
Social Stress ◽  
Subcutaneous Fat ◽  
Oral Glucose ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Homoeostasis ◽  
Peripheral Metabolism

Glucocorticoid overexposure during pregnancy programmes offspring physiology and predisposes to later disease. However, any impact of ethologically relevant maternal stress is less clear, yet of physiological importance. Here, we investigated in rats the short- and long-term effects in adult offspring of repeated social stress (exposure to an aggressive lactating female) during late pregnancy on glucose regulation following stress, glucose–insulin homoeostasis and peripheral expression of genes important in regulating glucose and lipid metabolism and glucocorticoid action. Prenatal stress (PNS) was associated with reduced birth weight in female, but not male, offspring. The increase in blood glucose with restraint was exaggerated in adult PNS males compared with controls, but not in females. Oral glucose tolerance testing showed no effects on plasma glucose or insulin concentrations in either sex at 3 months; however, at 6 months, PNS females were hyperinsulinaemic following an oral glucose load. In PNS males, plasma triglyceride concentrations were increased, with reduced hepatic mRNA expression of 5α-reductase and peroxisome proliferator-activated receptor α (Pparα(Ppara)) and a strong trend towards reduced peroxisome proliferator-activated receptor gamma coactivator 1α (Pgc1α(Ppargc1a)) andPparγ(Pparg) expression, whereas onlyPgc1αmRNA was affected in PNS females. Conversely, in subcutaneous fat, PNS reduced mRNA expression of 11β-hydroxysteroid dehydrogenase type 1 (11βhsd1), phosphoenolpyruvate carboxykinase (Pepck(Pck1)), adipose triglyceride lipase (Atgl) and diglyceride acyltransferase 2 (Dgat2) in females, but onlyPepckmRNA expression was reduced in PNS males. Thus, prenatal social stress differentially programmes glucose homoeostasis and peripheral metabolism in male and female offspring. These long-term alterations in physiology may increase susceptibility to metabolic disease.

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