Glucocorticoids as Mediators of Adverse Outcomes of Prenatal Stress

Krontira, Anthi C.; Cruceanu, Cristiana; Binder, Elisabeth B.

doi:10.1016/j.tins.2020.03.008

Cited by 74 publications

(70 citation statements)

References 91 publications

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“…The fetal HPA axis and limbic brain areas regulating the axis such as the hippocampus mature late in gestation (Wood and Walker, 2015). Overexposure of the fetal brain to maternal CORT increases negative feedback control of the axis to counter the effects of elevated maternal corticosterone (Krontira et al, 2020). PS was shown to decrease GR expression in the amygdala and hippocampus to a greater extent in the female fetus than in the male fetus (Lan et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Differences in DNA Methylation Reprogramming Underlie the Sexual Dimorphism of Behavioral Disorder Caused by Prenatal Stress in Rats

Lei

et al. 2020

Front. Neurosci.

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Prenatal stress (PS) can lead to neuroendocrine and emotional disorders later in adolescence. Sexual dimorphism in these neurodevelopmental outcomes have been observed; however, the underlying mechanisms are not fully understood. To address this issue, we investigated whether there are sex differences in epigenetic reprogramming in rats exposed to PS. Pregnant female rats were subjected to chronic restraint stress from gestational day (G)12 to G18. From postnatal day (P)38 to P45, subgroups of offspring including both males and females were subjected to behavioral testing and brain tissue specimens were analyzed by DNA pyrosequencing, western blotting, and Golgi staining to assess changes in methylation pattern of glucocorticoid receptor (GR) gene, expression of DNA methyltransferase (DNMT) and DNA demethylase, and dendrite morphology, respectively. The DNA methyltransferase inhibitor decitabine was administered to rats prior to PS to further evaluate the role of methylation in the sexually dimorphic effects of PS. The results showed that PS increased anxiety-like behavior in offspring, especially in females, while depression-like behavior was increased in male offspring compared to control littermates. The methylation pattern in the promoter region of the GR gene differed between males and females. Sex-specific changes in the expression of DNMTs (DNMT1 and DNMT3a) and DNA demethylase (Tet methylcytosine dioxygenase 2) were also observed. Interestingly, decitabine alleviated the behavioral disorder caused by PS and restored dendrite density and morphology in female but not male rats. These findings suggest that different change patterns of DNMT and demethylase in the two sexes after PS are responsible for the sexually dimorphism, which could have implications for the clinical management of stress-related disorders.

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Section: Discussionmentioning

confidence: 99%

Differences in DNA Methylation Reprogramming Underlie the Sexual Dimorphism of Behavioral Disorder Caused by Prenatal Stress in Rats

Lei

et al. 2020

Front. Neurosci.

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“…This emerging evidence suggests that some proportion of the mental health burden of current populations could reflect the lingering biological imprint of past traumatic experience during gestation (Barker 1999; Krontira et al 2020; Kuzawa & Sweet 2009). South Africa’s recent history and the country’s tumultuous transition into democracy raise the question of whether the traumas of Apartheid may continue to have lasting effects, influencing risk for psychiatric morbidity across generations (Kim 2020).…”

Section: Introductionmentioning

confidence: 99%

Psychological Legacies of Intergenerational Trauma under South African Apartheid: Prenatal Stress Predicts Increased Psychiatric Morbidity during Late Adolescence and Early Adulthood in Soweto, South Africa

Kim

Said‐Mohamed

Norris

et al. 2021

Preprint

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BackgroundSouth Africa’s rates of psychiatric morbidity are among the highest in sub-Saharan Africa and are foregrounded by the country’s long history of political violence during apartheid. Recent evidence suggests that maternal trauma during gestation may intergenerationally impact the developing fetus and elevate the future child’s risk for psychiatric disease. We aim to evaluate the intergenerational effects of prenatal stress experienced during apartheid on late adolescent psychiatric morbidity and also assess the potential ameliorative effects of prenatal social support.MethodParticipants (n = 1051) come from Birth-to-Twenty, a longitudinal birth cohort study in Soweto-Johannesburg, South Africa’s largest peri-urban township which was the epicenter of violent repression and resistance during the final years of the apartheid regime. Pregnant women were prospectively enrolled in 1990 and completed questionnaires assessing social experiences, and their children’s psychiatric morbidity were assessed at age 17-18.ResultsFull data were available from 304 mother-child pairs in 2007-8. Pregnant women who experienced worse traumatic stress in 1990 had children who exhibited greater psychiatric morbidity during late adolescence. This relationship was only significant, however, among children born to younger mothers and adolescents who experienced greater concurrent stress. Social support did not buffer the long-term impacts of prenatal stress on future psychiatric morbidity.ConclusionGreater prenatal stress predicted adverse psychiatric outcomes among children born to younger mothers and adolescents who experienced greater concurrent stress. Our findings suggest that prenatal stress may affect adolescent mental health, have stress-sensitizing effects, and represent possible intergenerational effects of trauma experienced under apartheid in this sample.

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“…Many studies suggest maternal depression during pregnancy can increase the cortisol level both in the pregnant women and fetus (26). Cortisol can stimulate production of CRH in the placenta (27).…”

Section: Discussionmentioning

confidence: 99%

Promoter Methylation Changes in the Placental DIO3 and CRH Genes Are Involved in the Second Trimester Maternal Depression Induced Preterm Birth and Small for Gestational Age Birth

Yang

Deng

Lin

et al. 2021

Preprint

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Background Recent studies suggest that the incidence of preterm birth and SGA birth related to maternal depression, but the mechanism is unclear. The aim of this study was to explore the placental epigenetic changes involved in maternal depression induced preterm birth and small for gestational age birth. Methods Three hundred forty-five pregnant women were enrolled in this cohort study. Maternal depression in the second and third trimesters was assessed using a self-rating depression scale (SDS). We selected placental samples from pregnant women with depression and an equivalent number for samples from pregnant women without depression. Methylation of the promoter regions of the placental DIO3 and CRH genes was determined using next generation sequencing based on bisulfite sequencing PCR (NGS-BSP). Results There were 97 (28.1%) and 95 (27.5%) pregnant women who had depression in the second trimester and third trimester, respectively. The risk factors of preterm birth were older maternal age (RR = 1.43, 95%CI = 1.01–2.03), uterine infection (RR = 129.31, 95%CI = 2.16-7725.55), and maternal depression in the second trimester (RR = 79.97, 95%CI = 3.57-1792.56). The risk factors of SGA birth were low maternal BMI (RR = 0.71, 95%CI = 0.54ཞ0.92), hypertensive disorder complicating pregnancy (HDCP, RR = 4.7, 95%CI = 1.18ཞ18.72), and maternal depression in the second trimester (RR = 3.71, 95%CI = 1.31ཞ12.16). Pregnant women with depression had higher placental methylation of CRH and DIO3 genes, and there was a correlation between placental methylation of CRH and DIO3 genes. Conclusion Our study suggested that the changes in the promoter region of the placental DIO3 and CRH genes were involved in maternal depression in the second trimester induced preterm birth and small for gestational age birth.

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Glucocorticoids as Mediators of Adverse Outcomes of Prenatal Stress

Cited by 74 publications

References 91 publications

Differences in DNA Methylation Reprogramming Underlie the Sexual Dimorphism of Behavioral Disorder Caused by Prenatal Stress in Rats

Differences in DNA Methylation Reprogramming Underlie the Sexual Dimorphism of Behavioral Disorder Caused by Prenatal Stress in Rats

Psychological Legacies of Intergenerational Trauma under South African Apartheid: Prenatal Stress Predicts Increased Psychiatric Morbidity during Late Adolescence and Early Adulthood in Soweto, South Africa

Promoter Methylation Changes in the Placental DIO3 and CRH Genes Are Involved in the Second Trimester Maternal Depression Induced Preterm Birth and Small for Gestational Age Birth

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Glucocorticoids as Mediators of Adverse Outcomes of Prenatal Stress

Cited by 74 publications

References 91 publications

Differences in DNA Methylation Reprogramming Underlie the Sexual Dimorphism of Behavioral Disorder Caused by Prenatal Stress in Rats

Differences in DNA Methylation Reprogramming Underlie the Sexual Dimorphism of Behavioral Disorder Caused by Prenatal Stress in Rats

Psychological Legacies of Intergenerational Trauma under South African Apartheid: Prenatal Stress Predicts Increased Psychiatric Morbidity during Late Adolescence and Early Adulthood in Soweto, South Africa

Promoter Methylation Changes in the Placental&nbsp;DIO3 and CRH Genes Are Involved in the Second Trimester Maternal Depression Induced Preterm Birth and Small for Gestational Age Birth

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Promoter Methylation Changes in the Placental DIO3 and CRH Genes Are Involved in the Second Trimester Maternal Depression Induced Preterm Birth and Small for Gestational Age Birth