Prenatal psychosocial stress-induced behavioral and neuroendocrine abnormalities are associated with sex-specific alterations in synaptic transmission and differentially modulated by maternal environment

Prenatal stress (PS) is associated with increased vulnerability to affective disorders. Transplacental glucocorticoid passage and stress-induced maternal environment alterations are recognized as potential routes of transmission that can fundamentally alter neurodevelopment. However, molecular mechanisms underlying aberrant emotional outcomes or the individual contributions intrauterine stress versus maternal environment play in shaping these mechanisms remain unknown. Here, we report anxiogenic behaviors, anhedonia, and female hypothalamic-pituitary-adrenal axis hyperactivity as a consequence of psychosocial PS in mice. Sex-specific placental responses to stress and evidence of fetal amygdala programming precede these abnormalities. In adult offspring, we observe amygdalar transcriptional changes demonstrating sex-specific dysfunction in synaptic transmission and neurotransmitter systems. We find these abnormalities are primarily driven by in-utero stress exposure. Importantly, maternal care changes postnatally reverse anxiety-related behaviors and partially rescue gene alterations associated with neurotransmission. Our data demonstrate the influence maternal environment exerts in shaping offspring emotional development despite deleterious effects of intrauterine stress.

• Publication year

  2020

• Venue

  bioRxiv

• Publication date

  2020-05-23

• Fields of study

  Biology, Medicine, Psychology

• Identifiers
  DOI 10.1101/2020.05.20.106674
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

• Chronic psychosocial stress during pregnancy affects maternal behavior and neuroendocrine function and modulates hypothalamic CRH and nuclear steroid receptor expression

  2020cited by this paper
• Sequence Analysis

  2020cited by this paper
• The adaptor proteins HAP1a and GRIP1 collaborate to activate the kinesin-1 isoform KIF5C

  2019cited by this paper
• AMPA receptors and their minions: auxiliary proteins in AMPA receptor trafficking

  2019influential reference
• Programming Effects of Prenatal Stress on Neurodevelopment—The Pitfall of Introducing a Self-Fulfilling Prophecy

  2019cited by this paper
• Varying Negative Pressure Wound Therapy Acute Effects on Human Split-Thickness Autografts.

  2019cited by this paper
• Intracerebral Hemorrhage Induces Inflammatory Gene Expression in Peripheral Blood: Global Transcriptional Profiling in Intracerebral Hemorrhage Patients

  2019cited by this paper
• Animal models of major depression: drawbacks and challenges

  2019cited by this paper
• Stress-Induced Functional Alterations in Amygdala: Implications for Neuropsychiatric Diseases

  2018cited by this paper
• Inflammation induces two types of inflammatory dendritic cells in inflamed lymph nodes

  2018cited by this paper
• Inhibition in the amygdala anxiety circuitry

  2018cited by this paper
• Genome-wide association study results for educational attainment aid in identifying genetic heterogeneity of schizophrenia

  2018cited by this paper
• Placental H3K27me3 establishes female resilience to prenatal insults

  2018cited by this paper
• Mild Prenatal Stress Causes Emotional and Brain Structural Modifications in Rats of Both Sexes

  2018cited by this paper
• Loss of Intercalated Cells (ITCs) in the Mouse Amygdala of Tshz1 Mutants Correlates with Fear, Depression, and Social Interaction Phenotypes

  2017cited by this paper
• Modeling the Sex Differences and Interindividual Variability in the Activity of the Hypothalamic-Pituitary-Adrenal Axis

  2017cited by this paper
• Sex differences in early-life programming of the hypothalamic-pituitary-adrenal axis in humans suggest increased vulnerability in females: a systematic review.

  2017influential reference
• Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally

  2017cited by this paper
• Targeting glutamate signalling in depression: progress and prospects

  2017cited by this paper
• Prenatal stressors in rodents: Effects on behavior

  2016cited by this paper
• Placental Nutrient Transport and Intrauterine Growth Restriction

  2016cited by this paper
• Enrichr: a comprehensive gene set enrichment analysis web server 2016 update

  2016influential reference
• Plants capable of selfing are more likely to become naturalized

  2016cited by this paper
• Fetal programming of neuropsychiatric disorders.

  2016cited by this paper
• GSG1L suppresses AMPA receptor-mediated synaptic transmission and uniquely modulates AMPA receptor kinetics in hippocampal neurons

  2016cited by this paper
• The Programming Power of the Placenta

  2016cited by this paper
• RUVSeq : Remove Unwanted Variation from RNA-Seq Data

  2016cited by this paper
• The placenta and neurodevelopment: sex differences in prenatal vulnerability

  2016cited by this paper
• Paraventricular Hypothalamic Mechanisms of Chronic Stress Adaptation

  2016cited by this paper
• Developmental manganese exposure in combination with developmental stress and iron deficiency: Effects on behavior and monoamines.

  2016cited by this paper
• The Placenta as a Mediator of Stress Effects on Neurodevelopmental Reprogramming

  2016cited by this paper
• Prenatal stress, regardless of concurrent escitalopram treatment, alters behavior and amygdala gene expression of adolescent female rats.

  2015cited by this paper
• Changes induced by prenatal stress in behavior and brain morphology: can they be prevented or reversed?

  2015cited by this paper
• The role of glucocorticoid receptor-dependent activity in the amygdala central nucleus and reversibility of early-life stress programmed behavior

  2015cited by this paper
• Prenatal immune challenge in rats: effects of polyinosinic-polycytidylic acid on spatial learning, prepulse inhibition, conditioned fear, and responses to MK-801 and amphetamine.

  2015cited by this paper
• Epigenetic and transgenerational reprogramming of brain development

  2015influential reference
• Biological and psychosocial predictors of postpartum depression: systematic review and call for integration.

  2015cited by this paper
• Peripubertal stress-induced behavioral changes are associated with altered expression of genes involved in excitation and inhibition in the amygdala

  2014cited by this paper
• Effects of maternal exposure to social stress during pregnancy: consequences for mother and offspring.

  2013influential reference
• 11β-hydroxysteroid dehydrogenases: intracellular gate-keepers of tissue glucocorticoid action.

  2013influential reference
• Effects of chronic social defeat on expression of dopamine β‐hydroxylase in rat brains

  2013cited by this paper
• The ERK1/2 Signaling Pathway Regulates 11beta-Hydroxysteroid Dehydrogenase Type 2 Expression in Human Trophoblast Cells Through a Transcriptional Mechanism1

  2013cited by this paper
• featureCounts: an efficient general purpose program for assigning sequence reads to genomic features

  2013cited by this paper
• Neurobehavioral phenotype of C57BL/6J mice prenatally and neonatally exposed to cigarette smoke.

  2013cited by this paper
• Transgenerational effects of infantile adversity and enrichment in male and female rats.

  2012cited by this paper
• Epigenetic Effects of Prenatal Stress on 11β-Hydroxysteroid Dehydrogenase-2 in the Placenta and Fetal Brain

  2012influential reference
• Sex-Specific Modulation of Gene Expression Networks in Murine Hypothalamus

  2012cited by this paper
• Synaptic regulation of the hypothalamic–pituitary–adrenal axis and its modulation by glucocorticoids and stress

  2012cited by this paper
• Anxiety-like behaviour and associated neurochemical and endocrinological alterations in male pups exposed to prenatal stress.

  2012cited by this paper
• Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation

  2012cited by this paper
• Functions of S100 proteins.

  2012cited by this paper
• Impaired AMPA Receptor Trafficking and Function by Mutant Huntingtin

  2011cited by this paper
• Altered placental development in undernourished rats: role of maternal glucocorticoids

  2011cited by this paper
• Vulnerability in early life to changes in the rearing environment plays a crucial role in the aetiopathology of psychiatric disorders.

  2011cited by this paper
• Impaired α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) Receptor Trafficking and Function by Mutant Huntingtin*

  2011cited by this paper
• From Stress to Postpartum Mood and Anxiety Disorders: How Chronic Peripartum Stress Can Impair Maternal Adaptations

  2011cited by this paper
• The GABAergic deficit hypothesis of major depressive disorder

  2011cited by this paper
• Differential Effect of Prenatal Stress on the Expression of Cortiocotrophin‐Releasing Hormone and its Receptors in the Hypothalamus and Amygdala in Male and Female Rats

  2011cited by this paper
• Glucocorticoids, prenatal stress and the programming of disease.

  2011cited by this paper
• Sex differences in synaptic plasticity in stress-responsive brain regions following chronic variable stress.

  2011cited by this paper
• Sex- and Diet-Specific Changes of Imprinted Gene Expression and DNA Methylation in Mouse Placenta under a High-Fat Diet

  2010cited by this paper
• Socioeconomic status and the brain: mechanistic insights from human and animal research

  2010cited by this paper
• Early life programming and neurodevelopmental disorders.

  2010cited by this paper
• Prenatal Social Stress in the Rat Programmes Neuroendocrine and Behavioural Responses to Stress in the Adult Offspring: Sex‐Specific Effects

  2010cited by this paper
• Prenatal stress and the programming of the HPA axis.

  2010cited by this paper
• Prenatal stress reduces postnatal neurogenesis in rats selectively bred for high, but not low, anxiety: possible key role of placental 11β‐hydroxysteroid dehydrogenase type 2

  2009cited by this paper
• Sex-specific alterations in placental 11beta-hydroxysteroid dehydrogenase 2 activity and early postnatal clinical course following antenatal betamethasone.

  2009cited by this paper
• Effect of an acute maternal stress on the fetal hypothalamo-pituitary-adrenal system in late gestational life of the rat.

  2009cited by this paper
• Prenatal stress programming of offspring feeding behavior and energy balance begins early in pregnancy.

  2009cited by this paper
• Changes in the Placental Glucocorticoid Barrier During Rat Pregnancy: Impact on Placental Corticosterone Levels and Regulation by Progesterone1

  2009cited by this paper
• The long-term behavioural consequences of prenatal stress.

  2008cited by this paper
• Sex-Specific Programming of Offspring Emotionality after Stress Early in Pregnancy

  2008cited by this paper
• Role of the placenta in fetal programming: underlying mechanisms and potential interventional approaches.

  2007cited by this paper
• Prenatal stress increases HPA axis activity and impairs maternal care in lactating female offspring: implications for postpartum mood disorder.

  2007cited by this paper
• Mechanisms of Disease: glucocorticoids, their placental metabolism and fetal 'programming' of adult pathophysiology

  2007cited by this paper
• Prenatal psychological stress causes higher emotionality, depression-like behavior, and elevated activity in the hypothalamo-pituitary-adrenal axis.

  2007cited by this paper
• Adult mouse brain gene expression patterns bear an embryologic imprint.

  2005cited by this paper
• Cortisol in Mood Disorders

  2004cited by this paper
• Materno-fetal coordination of stress-induced Fos expression in the hypothalamic paraventricular nucleus during pregnancy.

  2003cited by this paper
• Glucocorticoids and sex-dependent development of brain glucocorticoid and mineralocorticoid receptors.

  2003cited by this paper
• Maternal Undernutrition during Late Gestation Induces Fetal Overexposure to Glucocorticoids and Intrauterine Growth Retardation, and Disturbs the Hypothalamo-Pituitary Adrenal Axis in the Newborn Rat.

  2001influential reference
• Prenatal Stress Induces High Anxiety and Postnatal Handling Induces Low Anxiety in Adult Offspring: Correlation with Stress-Induced Corticosterone Secretion

  1997cited by this paper
• Dimorphic expression of calbindin-D28K in the medial basal hypothalamus from perinatal male and female rats.

  1996cited by this paper
• Adoption reverses the long-term impairment in glucocorticoid feedback induced by prenatal stress

  1995cited by this paper

• No citing papers are available for this paper.