Maternal Prenatal Anxiety and the Fetal Origins of Epigenetic Aging

McGill, Megan; Pokhvisneva, Irina; Clappison, Andrew; McEwen, Lisa M.; Beijers, Roseriet; Tollenaar, Marieke S.; Pham, Hung; Kee, Michelle Z. L.; Garg, Elika; Filho, Euclides José de Mendonça; Karnani, Neerja; Silveira, Patrícia Pelufo; Kobor, Michæl S.; Weerth, Carolina de; Meaney, Michael J.; O’Donnell, Kieran J.

doi:10.1016/j.biopsych.2021.07.025

Cited by 42 publications

(31 citation statements)

References 43 publications

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“…Here, we adopted indirect markers of prenatal glucocorticoid and inflammation exposure, obtained by DNAm levels in sensitive CpGs sites. Previously, using two different cohorts, prenatal anxiety was not associated with the epigenetic proxy of glucocorticoid exposure [ 6 ]. In our findings, maternal feeling related to pregnancy was not a GAA predictor in the model considering the GES, being significant only in the i-ePGS model, even though the presence of maternal history of mental disorder contributed to both models.…”

Section: Discussionmentioning

confidence: 99%

“…To detect overexposure to inflammation or glucocorticoids during gestation requires complex study designs and it is challenging matter. As DNAm presents marks of environmental experiences, some studies have proposed epigenetic scores that can reflect these exposures [ 6 , 7 ]. DNAm in specific CpGs can also be used to build epigenetic clocks capable of predicting the chronological age of a sample with relative accuracy [ 5 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…Inflammatory pathways are also critical and fundamental for fetal development, but overexposure to inflammatory markers appears to be predictors of worse obstetric and postnatal outcomes [ 20 , 21 ]. Epigenetic mechanisms have been proposed as mediators in this context for a long time [ 3 , 6 ]. Barker et al [ 7 ] replicate an inflammation epigenetic polygenic score (i-ePGS), as a marker of low-grade inflammation exposure in a developmentally sensitive framework.…”

Section: Introductionmentioning

confidence: 99%

“…We and others [ 29 , 30 ] have provided evidence of sex bias in cord blood DNA methylation. Recently McGill et al [ 6 ] showed that prenatal maternal anxiety predicted infant AA (PedBE algorithm) in two cohorts, independent of obstetric, socioeconomic, and genetic risk factors. Also, AA predicted increased externalizing symptoms in males from mid- to late childhood in one of the two cohorts.…”

Section: Introductionmentioning

confidence: 99%

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Gestational age acceleration is associated with epigenetic biomarkers of prenatal physiologic stress exposure

et al. 2022

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Background Physiological maternal stress response, such as imbalance in the glucocorticoid pathway and immune system seems to be mediated by DNA methylation (DNAm) and might translate intrauterine stress exposures into phenotypic changes in a sex-specific manner. DNAm in specific sites can also predict newborn gestational age and gestational age acceleration (GAA). GAA occurs when the predicted biological age is higher than the chronological age. In adults, poor health outcomes related to this deviance are well documented and raise questions for the interpretation and prediction in early stages of life. Boys seem to be more vulnerable to intrauterine stress exposure than girls; however, the mechanisms of adaptive sex-specific responses are still unclear. We hypothesize that intrauterine stress exposure is associated with GAA and could be different in boys and girls if inflammatory or glucocorticoid pathways exposure is considered. Results Using the Western Region Birth Cohort (ROC—São Paulo, Brazil) (n = 83), we calculated DNAm age and GAA from cord blood samples. Two epigenetic risk scores were calculated as an indirect proxy for low-grade inflammation (i-ePGS) and for glucocorticoid exposure (GES). Multivariate linear regression models were applied to investigate associations of GAA with prenatal exposures. The i-ePGS and GES were included in different models with the same co-variates considering sex interactions. The first multivariate model investigating inflammatory exposure (adj. R2 = 0.31, p = < 0.001) showed that GAA was positively associated with i-ePGS (CI, 0.26–113.87, p = 0.049) and negative pregnancy-related feelings (CI, 0.04–0.48 p = 0.019). No sex interaction was observed. The second model investigating glucocorticoid exposure (adj. R2 = 0.32, p = < 0.001) showed that the higher was the GAA was associated with a lower the lower was the GES in girls (CI, 0.04–2.55, p = 0.044). In both models, maternal self-reported mental disorder was negatively associated with GAA. Conclusion Prenatal epigenetic score of exposure to low-grade inflammatory was a predictor of GAA for both sexes. Glucocorticoid epigenetic score seems to be more important to GAA in girls. This study supports the evidence of sex-specificity in stress response, suggesting the glucocorticoid as a possible pathway adopted by girls to accelerate the maturation in an adverse condition.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Gestational age acceleration is associated with epigenetic biomarkers of prenatal physiologic stress exposure

et al. 2022

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“…Numerous animal studies have shown that long-lasting epigenetic changes caused by prenatal stress involve gene encoding BNDF, the corticotropin-releasing factor (Crf), and the glucocorticoid receptor (Nr3c1), which is associated with the HPA axis (Mueller and Bale, 2008 ; Dong et al, 2015 ). Recent clinical studies have found that prenatal maternal anxiety predicts accelerated epigenetic age in children in the experimental cohort and reveals increased sensitivity in men rather than woman in regared to the fetal origins of epigenetic age acceleration (Mcgill et al, 2022 ).…”

Section: The Effects Of Ee On Neurodevelopment In Brainmentioning

confidence: 99%

The role of enriched environment in neural development and repair

Yuan

Guo

Shen

et al. 2022

Front. Cell. Neurosci.

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In addition to genetic information, environmental factors play an important role in the structure and function of nervous system and the occurrence and development of some nervous system diseases. Enriched environment (EE) can not only promote normal neural development through enhancing neuroplasticity but also play a nerve repair role in restoring functional activities during CNS injury by morphological and cellular and molecular adaptations in the brain. Different stages of development after birth respond to the environment to varying degrees. Therefore, we systematically review the pro-developmental and anti-stress value of EE during pregnancy, pre-weaning, and “adolescence” and analyze the difference in the effects of EE and its sub-components, especially with physical exercise. In our exploration of potential mechanisms that promote neurodevelopment, we have found that not all sub-components exert maximum value throughout the developmental phase, such as animals that do not respond to physical activity before weaning, and that EE is not superior to its sub-components in all respects. EE affects the developing and adult brain, resulting in some neuroplastic changes in the microscopic and macroscopic anatomy, finally contributing to enhanced learning and memory capacity. These positive promoting influences are particularly prominent regarding neural repair after neurobiological disorders. Taking cerebral ischemia as an example, we analyzed the molecular mediators of EE promoting repair from various dimensions. We found that EE does not always lead to positive effects on nerve repair, such as infarct size. In view of the classic issues such as standardization and relativity of EE have been thoroughly discussed, we finally focus on analyzing the essentiality of the time window of EE action and clinical translation in order to devote to the future research direction of EE and rapid and reasonable clinical application.

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Prenatal Maternal Occupation and Child Epigenetic Age Acceleration in an Agricultural Region

Daredia,

Bozack,

Riddell

et al. 2024

JAMA Netw Open

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ImportanceResearch on fetal epigenetic programming suggests that the intrauterine environment can have long-term effects on offspring disease susceptibility.ObjectiveTo examine the association between prenatal maternal occupation and child epigenetic age acceleration (EAA) among a farmworker community.Design, Setting, and ParticipantsThis cohort study included participants in the Center for the Health Assessment of Mothers and Children of Salinas, a prospective, Latino, prebirth cohort. Pregnant women were recruited from October 1, 1999, to October 1, 2000, from 6 community clinics in California’s Salinas Valley agricultural region. Participants were 18 years or older, English or Spanish speaking, Medicaid eligible, and at 20 weeks’ gestation or earlier at enrollment. Mother-child pairs who had blood DNA methylation measured at the ages of 7, 9, and 14 years were included. Data were analyzed from July 2021 to November 2023.ExposuresPrenatal maternal occupation was ascertained through study interviews conducted during prenatal visits and shortly after delivery.Main Outcomes and MeasuresChild EAA at 7, 9, and 14 years of age was estimated using DNA methylation–based epigenetic age biomarkers. Three EAA measures were calculated: the Horvath EAA, skin and blood EAA, and intrinsic EAA. Linear mixed-effects models were used to estimate longitudinal associations of prenatal maternal occupation and child EAA, adjusting for confounders and prenatal organophosphate pesticide exposure.ResultsAnalyses included 290 mother-child pairs (mean [SD] maternal age at delivery, 26.5 [5.2] years; 152 [52.4%] female infants); 254 mothers (87.6%) were born in Mexico, 33 (11.4%) in the US, and 3 (1.0%) in other countries; and 179 families (61.7%) were below the federal poverty line during pregnancy. Mothers reported engaging in several types of work during pregnancy, including agricultural fieldwork (90 [31.0%]), other agricultural work (40 [13.8%]), nonagricultural work (53 [18.3%]), or no work (107 [36.9%]). Children whose mothers worked in agricultural fields during pregnancy had a mean of 0.66 (95% CI, 0.17-1.15) years of greater Horvath EAA, 0.62 (95% CI, 0.31-0.94) years of greater skin and blood EAA, and 0.45 (95% CI, 0.07-0.83) years of greater intrinsic EAA compared with children whose mothers did not work during pregnancy.Conclusions and RelevanceIn this cohort study, prenatal maternal agricultural fieldwork was associated with accelerated childhood epigenetic aging independent of organophosphate pesticide exposure. Future research on which factors related to agricultural fieldwork accelerate aging in the next generation can inform targeted prevention programs and policies that protect children’s health.

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Maternal Prenatal Anxiety and the Fetal Origins of Epigenetic Aging

Cited by 42 publications

References 43 publications

Gestational age acceleration is associated with epigenetic biomarkers of prenatal physiologic stress exposure

Gestational age acceleration is associated with epigenetic biomarkers of prenatal physiologic stress exposure

The role of enriched environment in neural development and repair

Prenatal Maternal Occupation and Child Epigenetic Age Acceleration in an Agricultural Region

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