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Background/objectives: Prenatal exposure to ambient air pollution is associated with adverse cardiometabolic outcomes in childhood. We previously observed that prenatal black carbon (BC) was inversely associated with adiponectin, a hormone secreted by adipocytes, in early childhood. Changes to DNA methylation have been proposed as a potential mediator linking in utero exposures to lasting health impacts.
Methods: Among 532 mother-child pairs enrolled in the Colorado-based Healthy Start study, we performed an epigenome-wide association study of the relationship between prenatal exposure to a component of air pollution, BC, and DNA methylation in cord blood. Average pregnancy ambient BC was estimated at the mother's residence using a spatiotemporal prediction model. DNA methylation was measured using the Illumina 450K array. We used multiple linear regression to estimate associations between prenatal ambient BC and 429,246 cysteine-phosphate-guanine sites (CpGs), adjusting for potential confounders. We identified differentially methylated regions (DMRs) using DMRff and ENmix-combp. In a subset of participants (n = 243), we investigated DNA methylation as a potential mediator of the association between prenatal ambient BC and lower adiponectin in childhood.
Results: We identified 44 CpGs associated with average prenatal ambient BC after correcting for multiple testing. Several genes annotated to the top CpGs had reported functions in the immune system. There were 24 DMRs identified by both DMRff and ENmix-combp. One CpG (cg01123250), located on chromosome 2 and annotated to the UNC80 gene, was found to mediate approximately 20% of the effect of prenatal BC on childhood adiponectin, though the confidence interval was wide (95% CI: 3, 84).
Conclusions: Prenatal BC was associated with DNA methylation in cord blood at several sites and regions in the genome. DNA methylation may partially mediate associations between prenatal BC and childhood cardiometabolic outcomes.
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http://dx.doi.org/10.1016/j.ijheh.2024.114464 | DOI Listing |
Mol Psychiatry
September 2025
Department of Child and Adolescent Psychiatry and Psychology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.
Epigenetic processes, such as DNA methylation, show potential as biological markers and mechanisms underlying gene-environment interplay in the prediction of mental health and other brain-based phenotypes. However, little is known about how peripheral epigenetic patterns relate to individual differences in the brain itself. An increasingly popular approach to address this is by combining epigenetic and neuroimaging data; yet, research in this area is almost entirely comprised of cross-sectional studies in adults.
View Article and Find Full Text PDFMod Pathol
September 2025
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. Electronic address:
Uterine leiomyosarcoma (uLMS) is a rare and deadly gynecologic malignancy. uLMS is histologically heterogeneous and presents with a wide spectrum of tumor differentiation, with a broad range of genomic DNA instability, which can make the diagnosis and prognosis of uLMS challenging. Methylation has emerged as a useful molecular tool in tumor classification and diagnosis in certain neoplasms.
View Article and Find Full Text PDFMol Cell Endocrinol
September 2025
Department of Epidemiology, University of Michigan, Ann Arbor, USA. Electronic address:
Steroid hormones are integral to pregnancy and fetal development, regulating processes such as metabolism, inflammation, and immune responses. Excessive prenatal steroid exposure, through lifestyle choices or environmental chemicals, can lead to metabolic dysfunctions in offspring. The research focuses on how exposure to testosterone (T) and bisphenol A (BPA) affects the liver's DNA methylome, a key component of the epigenome influencing long-term health.
View Article and Find Full Text PDFJ Biol Chem
September 2025
Department of Biological Sciences, Ohio University, Athens, Ohio, United States of America; Molecular and Cellular Biology Graduate Program, Ohio University, Athens, Ohio, United States of America. Electronic address:
Temozolomide (TMZ), a DNA alkylator, is a chemotherapeutic agent for brain tumors, but the treatment induces a distinct pattern of mutations, known as a cancer mutational signature SBS11. Although the correlation between TMZ treatment and SBS11 mutations is very clear, the precise biochemical mechanisms that cause SBS11 have not been elucidated. TMZ can alkylate DNA at several locations, among which O-methylguanine (Ome-G) is believed to be most toxic.
View Article and Find Full Text PDFCell Rep
September 2025
Institut Curie, UMR3348, CNRS, Université Paris-Saclay, 91401 Orsay, France. Electronic address:
Alternative splicing enables cells to acquire novel phenotypic traits for adaptation to changes in the environment. However, the mechanisms that allow these dynamic changes to occur in a timely and sustained manner remain unknown. Recent investigations unveiled a new regulatory layer important for splicing dynamics and memory: the chromatin.
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