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

Euclydes, V. and Gomes, C. and Gouveia, G. and Gastaldi, V. D. and Feltrin, A. S. and Camilo, C. and Vieira, R. P. and Felipe-Silva, A. and Grisi, S. and Fink, G. and Brentani, A. and Brentani, H.. (2022) Gestational age acceleration is associated with epigenetic biomarkers of prenatal physiologic stress exposure. Clin Epigenetics, 14. p. 152.

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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-Sao 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. R(2) = 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. R(2) = 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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Household Economics and Health Systems Research > Epidemiology and Household Economics (Fink)
06 Faculty of Business and Economics > Departement Wirtschaftswissenschaften > Professuren Wirtschaftswissenschaften > Epidemiology and Household Economics (Fink)
UniBasel Contributors:Fink, G√ľnther
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1868-7083 (Electronic)1868-7075 (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:28 Dec 2022 10:35
Deposited On:28 Dec 2022 10:35

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