Agueda Castro-Quintas , Helena Palma-Gudiel , Elisenda Eixarch , Nerea San Martín González , Simone Röh , Susann Sauer , Monika Rex-Haffner , Jose Luis Monteserin-Garcia , Lorena de la Fuente-Tomás , Fatima Crispi , Maria Paz Garcia Portilla , Elisabeth B. Binder , Lourdes Fañanas
{"title":"Placental epigenetic signatures of maternal distress in glucocorticoid-related genes and newborn outcomes: A study of Spanish primiparous women","authors":"Agueda Castro-Quintas , Helena Palma-Gudiel , Elisenda Eixarch , Nerea San Martín González , Simone Röh , Susann Sauer , Monika Rex-Haffner , Jose Luis Monteserin-Garcia , Lorena de la Fuente-Tomás , Fatima Crispi , Maria Paz Garcia Portilla , Elisabeth B. Binder , Lourdes Fañanas","doi":"10.1016/j.euroneuro.2024.10.001","DOIUrl":null,"url":null,"abstract":"<div><div>Maternal stress during pregnancy can impact offspring health, increasing the risk of neuropsychiatric disorders. The human placenta plays a crucial role in understanding this effect, influencing fetal programming as it connects maternal and fetal circulation. Our hypothesis centers on maternal stress influencing children's outcomes through placental DNA methylation, targeting three cortisol-regulating genes: <em>NR3C1, FKBP5</em>, and <em>HSD11B2</em>.</div><div>In this pilot study, chorionic villi and maternal decidua placental layers from 45 mother-infant dyads (divided into two groups based on high/low maternal stress exposure) were analyzed for DNA methylation at the genes of interest via targeted bisulfite sequencing. Pregnant women provided four saliva samples throughout a day for cortisol determinations and were assessed for the presence of depressive symptoms at each of the three trimesters of pregnancy. Newborns underwent neurodevelopmental assessments and salivary cortisol evaluations at 7 weeks.</div><div>Increased maternal diurnal cortisol levels in the first trimester of pregnancy was significantly associated with elevated DNA methylation at exon 1D of the <em>NR3C1</em> gene and lower DNA methylation at intron 7 of the <em>FKBP5</em> gene, both in chorionic villi samples. Elevated DNA methylation at introns 1 and 7 of <em>FKBP5</em> in the maternal decidua were strongly linked to an anticipated delivery. DNA methylation at the <em>HSD11B2</em> promoter region was uniformly low across all placental samples. No associations with newborn neurodevelopment were found.</div><div>These results emphasize the importance of exploring layer-specific methylation differences at distinct pregnancy stages, highlighting the complex interplay between maternal stress, placental epigenetic modifications, and fetal development throughout the prenatal period.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":"90 ","pages":"Pages 36-47"},"PeriodicalIF":6.1000,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Neuropsychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0924977X24007375","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Maternal stress during pregnancy can impact offspring health, increasing the risk of neuropsychiatric disorders. The human placenta plays a crucial role in understanding this effect, influencing fetal programming as it connects maternal and fetal circulation. Our hypothesis centers on maternal stress influencing children's outcomes through placental DNA methylation, targeting three cortisol-regulating genes: NR3C1, FKBP5, and HSD11B2.
In this pilot study, chorionic villi and maternal decidua placental layers from 45 mother-infant dyads (divided into two groups based on high/low maternal stress exposure) were analyzed for DNA methylation at the genes of interest via targeted bisulfite sequencing. Pregnant women provided four saliva samples throughout a day for cortisol determinations and were assessed for the presence of depressive symptoms at each of the three trimesters of pregnancy. Newborns underwent neurodevelopmental assessments and salivary cortisol evaluations at 7 weeks.
Increased maternal diurnal cortisol levels in the first trimester of pregnancy was significantly associated with elevated DNA methylation at exon 1D of the NR3C1 gene and lower DNA methylation at intron 7 of the FKBP5 gene, both in chorionic villi samples. Elevated DNA methylation at introns 1 and 7 of FKBP5 in the maternal decidua were strongly linked to an anticipated delivery. DNA methylation at the HSD11B2 promoter region was uniformly low across all placental samples. No associations with newborn neurodevelopment were found.
These results emphasize the importance of exploring layer-specific methylation differences at distinct pregnancy stages, highlighting the complex interplay between maternal stress, placental epigenetic modifications, and fetal development throughout the prenatal period.
期刊介绍:
European Neuropsychopharmacology is the official publication of the European College of Neuropsychopharmacology (ECNP). In accordance with the mission of the College, the journal focuses on clinical and basic science contributions that advance our understanding of brain function and human behaviour and enable translation into improved treatments and enhanced public health impact in psychiatry. Recent years have been characterized by exciting advances in basic knowledge and available experimental techniques in neuroscience and genomics. However, clinical translation of these findings has not been as rapid. The journal aims to narrow this gap by promoting findings that are expected to have a major impact on both our understanding of the biological bases of mental disorders and the development and improvement of treatments, ideally paving the way for prevention and recovery.