Sex-based differences in placental DNA methylation profiles related to gestational age: an NIH ECHO meta-analysis

• Type of Material: Article
• Authors: Catherine MM Bulka, University of North Carolina; Todd Everson, Emory University; Amber A Burt, Emory University; Carmen Marsit, Emory University; Margaret R Karagas, Geisel School of Medicine at Dartmouth; Kristen E Boyle, University of Colorado Anschutz Medical Campus, Aurora; Sierra Niemiec, Colorado School of Public Health; Katerina Kechris, Colorado School of Public Health; Elizabeth J Davidson, University of Colorado, Aurora; Ivana V Yang, Colorado School of Public Health; Jason II Feinberg, Johns Hopkins Bloomberg School of Public Health; Heather E Volk, Johns Hopkins Bloomberg School of Public Health; Christine Ladd-Acosta, Johns Hopkins Bloomberg School of Public Health; Carrie V Breton, University of Southern California; Michaek T O'Shea, University of North Carolina Chapel Hill; Rebecca C Fry, University of North Carolina Chapel Hill
• Language: English
• Date: 2023-12-31
• Publisher: TAYLOR & FRANCIS INC
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1080/15592294.2023.2179726
• Title of Journal or Parent Work: EPIGENETICS
• Volume: 18
• Issue: 1
• Start Page: 2179726
• End Page: 2179726
• Grant/Funding Information: Research reported in this publication was supported by the Environmental influences on Child Health Outcomes (ECHO) programme, Office of The Director, National Institutes of Health, under Award Numbers U2COD023375 (Coordinating Center), UH3OD023348 U24OD023382 (Data Analysis Center), and U24OD023319 (PRO Core). The EARLI study was supported by the National Institutes of Health, under Award Number UH3OD023342 (Craig Newschaffer and Heather Volk). The ELGAN-ECHO study was supported by the National Institutes of Health, under Award Number UH3OD023348 (Rebecca C. Fry and T. Michael O’Shea). The Healthy Start Study was supported by the National Institutes of Health, under Award Numbers R01DK076648 and UG3OD023248 (Dana Dabelea), and by the Colorado Clinical and Translational Sciences Institute via National Institutes of Health, National Center for Advancing Translational Sciences for maternal visits and collection of birth measures, under Award Number UL1TR001082 (Ronald J. Sokol). The New Hampshire Birth Cohort Study was supported by the National Institutes of Health, under Award Numbers UH3OD023275 and P42ES007373 (Margaret Karagas) and P01ES022832 (Margaret Karagas and Carmen Marsit). Todd Everson and Carmen Marsit were additionally supported by the National Institutes of Health, under Award Number funded under Awarded Number UH3OD023347 (Barry Lester and Carmen Marsit). Carrie Breton was supported by the National Institutes of Health, under Award Number UH3OD023287 (Carrie Breton). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
• Keywords: NEUROLOGIC OUTCOMES; Genetics & Heredity; DISCOVERY; GENE-EXPRESSION; MEMBRANES; PREGNANCY; SUSCEPTIBILITY; MORTALITY; ASSOCIATION; sex differences; gestational age; Placenta; DNA methylation; MODELS; Biochemistry & Molecular Biology; Life Sciences & Biomedicine; PREECLAMPSIA; Science & Technology
• Research Categories: Health Sciences, Nutrition; Health Sciences, Epidemiology; Health Sciences, Public Health

Abstract

The placenta undergoes many changes throughout gestation to support the evolving needs of the foetus. There is also a growing appreciation that male and female foetuses develop differently in utero, with unique epigenetic changes in placental tissue. Here, we report meta-analysed sex-specific associations between gestational age and placental DNA methylation from four cohorts in the National Institutes of Health (NIH) Environmental influences on Child Health Outcomes (ECHO) Programme (355 females/419 males, gestational ages 23–42 weeks). We identified 407 cytosine-guanine dinucleotides (CpGs) in females and 794 in males where placental methylation levels were associated with gestational age. After cell-type adjustment, 55 CpGs in females and 826 in males were significant. These were enriched for biological processes critical to the immune system in females and transmembrane transport in males. Our findings are distinct between the sexes: in females, associations with gestational age are largely explained by differences in placental cellular composition, whereas in males, gestational age is directly associated with numerous alterations in methylation levels.