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Gestational age acceleration is associated with epigenetic biomarkers of prenatal physiologic stress exposure.
Euclydes, Verônica; Gomes, Catarina; Gouveia, Gisele; Gastaldi, Vinicius Daguano; Feltrin, Arthur Sant'Anna; Camilo, Caroline; Vieira, Rossana Pulcineli; Felipe-Silva, Aloísio; Grisi, Sandra; Fink, Günther; Brentani, Alexandra; Brentani, Helena.
Afiliación
  • Euclydes V; Department and Institute of Psychiatry, University of São Paulo Medical School, Rua Dr. Ovídio Pires de Campos, 785, LIM23 (Térreo), São Paulo, 05403-010, Brazil. veronicaeuclydes@alumni.usp.br.
  • Gomes C; Laboratório de Psicopatologia e Terapêutica Psiquiátrica (LIM23), Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil. veronicaeuclydes@alumni.usp.br.
  • Gouveia G; Department and Institute of Psychiatry, University of São Paulo Medical School, Rua Dr. Ovídio Pires de Campos, 785, LIM23 (Térreo), São Paulo, 05403-010, Brazil.
  • Gastaldi VD; Laboratório de Psicopatologia e Terapêutica Psiquiátrica (LIM23), Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil.
  • Feltrin AS; Department and Institute of Psychiatry, University of São Paulo Medical School, Rua Dr. Ovídio Pires de Campos, 785, LIM23 (Térreo), São Paulo, 05403-010, Brazil.
  • Camilo C; Laboratório de Psicopatologia e Terapêutica Psiquiátrica (LIM23), Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil.
  • Vieira RP; Department and Institute of Psychiatry, University of São Paulo Medical School, Rua Dr. Ovídio Pires de Campos, 785, LIM23 (Térreo), São Paulo, 05403-010, Brazil.
  • Felipe-Silva A; Laboratório de Psicopatologia e Terapêutica Psiquiátrica (LIM23), Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil.
  • Grisi S; Center of Mathematics, Computation and Cognition, Federal University of ABC, São Bernardo do Campo, Brazil.
  • Fink G; Department and Institute of Psychiatry, University of São Paulo Medical School, Rua Dr. Ovídio Pires de Campos, 785, LIM23 (Térreo), São Paulo, 05403-010, Brazil.
  • Brentani A; Laboratório de Psicopatologia e Terapêutica Psiquiátrica (LIM23), Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil.
  • Brentani H; Departamento de Obstetrícia e Ginecologia, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
Clin Epigenetics ; 14(1): 152, 2022 11 28.
Article en En | MEDLINE | ID: mdl-36443840
ABSTRACT

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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Metilación de ADN / Glucocorticoides Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Newborn / Pregnancy País/Región como asunto: America do sul / Brasil Idioma: En Revista: Clin Epigenetics Año: 2022 Tipo del documento: Article País de afiliación: Brasil

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Metilación de ADN / Glucocorticoides Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Newborn / Pregnancy País/Región como asunto: America do sul / Brasil Idioma: En Revista: Clin Epigenetics Año: 2022 Tipo del documento: Article País de afiliación: Brasil
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