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2019-05-09

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cc-by (c) Palma-Gudiel, Helena et al., 2019
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/159602

Prenatal adverse environment is associated with epigenetic age deceleration at birth and hypomethylation at the hypoxia-responsive EP300 gene

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https://doi.org/10.1186/s13148-019-0674-5

Resum

Abstract Background: Obstetric complications have long been retrospectively associated with a wide range of short- and long-term health consequences, including neurodevelopmental alterations such as those observed in schizophrenia and other psychiatric disorders. However, prospective studies assessing fetal well-being during pregnancy tend to focus on perinatal complications as the final outcome of interest, while there is a scarcity of postnatal follow-up studies. In this study, the cerebroplacental ratio (CPR), a hemodynamic parameter reflecting fetal adaptation to hypoxic conditions, was analyzed in a sample of monozygotic monochorionic twins (60 subjects), part of them with prenatal complications, with regard to (i) epigenetic age acceleration, and (ii) DNA methylation at genes included in the polygenic risk score (PRS) for schizophrenia, and highly expressed in placental tissue. Results: Decreased CPR measured during the third trimester was associated with epigenetic age deceleration (β = 0.21, t = 3.362, p = 0.002). Exploration of DNA methylation at placentally expressed genes of the PRS for schizophrenia revealed methylation at cg06793497 (EP300 gene) to be associated with CPR (β = 0.021, t = 4.385; p = 0.00008, FDR-adjusted p = 0.11). This association was reinforced by means of an intrapair analysis in monozygotic twins discordant for prenatal suffering (β = 0.027, t = 3.924, p = 0.001). Conclusions: Prenatal adverse environment during the third trimester of pregnancy is associated with both (i) developmental immaturity in terms of epigenetic age, and (ii) decreased CpG-specific methylation in a gene involved in hypoxia response and schizophrenia genetic liability. Keywords: DNA methylation, Obstetric complications, Prenatal stress, Hypoxia, EP300 gene, Epigenetic clock, Monozygotic twins, Schizophrenia

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Oxigen, Embaràs, Malalties mentals

Matèries (anglès)

Oxygen, Pregnancy, Mental illness

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Col·leccions

Articles publicats en revistes (Biologia Evolutiva, Ecologia i Ciències Ambientals)
Articles publicats en revistes (BCNatal Fetal Medicine Research Center)
Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

PALMA GUDIEL, Helena, EIXARCH ROCA, Elisenda, CRISPI BRILLAS, Fàtima, MORÁN, Sebastián, ZANNAS, Anthony s., FAÑANÁS SAURA, Lourdes. Prenatal adverse environment is associated with epigenetic age deceleration at birth and hypomethylation at the hypoxia-responsive EP300 gene. _Clinical Epigenetics_. 2019. Vol. 11, núm. 73. [consulta: 20 de gener de 2026]. ISSN: 1868-7075. [Disponible a: https://hdl.handle.net/2445/159602]

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