Dataset Information

Placental DNA methylation gene networks correlate with wildfire-informed particulate matter exposure and child neurodevelopment outcomes.

ABSTRACT: Background: Particulate air pollution represents an increasingly prominent prenatal exposure in the western United States, particularly in regions afflicted with heightened wildfire severity. However, the epigenetic impact of these exposures on the placenta remains poorly characterized. Objectives: We investigated whether prenatal exposure to particulate air pollution, from both ambient sources and wildfires, associate with coordinated alterations in placental DNA methylation networks. Methods: We performed whole-genome bisulfite sequencing (WGBS) on 221 placentae from the MARBLES and B-SAFE, then performed comethylation network analysis to identify modules of correlated DNA methylation associated with wilfire-informed particulate exposures and neurodevelopmental outcomes. Results: We identified 85 placental comethylation modules, 22 of which were significantly associated with prenatal air pollution exposures. Preconception and pregnancy exposures associated with distinct module sets. Pregnancy air pollution preferentially correlated with modules annotated to semaphorin signaling and cytoskeletal remodeling pathways, including SEMA3A and RND3. In contrast, preconception exposures were enriched for modules proximal to transcriptional regulators. Ten exposure-associated modules also correlated with child neurodevelopmental measures, including ASD diagnosis. These modules contained neurodevelopmentally relevant genes, including NHIP, AUTS2, EBF3, PLCB1, and SLIT2, and were enriched for synaptic and cell-cell signaling pathways. Conclusions: Prenatal air pollution exposure associates with temporally and source-specific placental methylation networks enriched for signaling pathways relevant to placental function and neurodevelopment. These findings support the placenta as an epigenetic interface linking air pollution exposure to altered developmental trajectories.

ORGANISM(S): Homo sapiens

PROVIDER: GSE324959 | GEO | 2026/07/30

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background: Epidemiologic associations between acutely increased cardiorespiratory morbidity and mortality and particulate air pollution are well-established, but the effects of acute pollution exposure on human gene expression changes are not well understood. Objectives: In order to identify potential mechanisms underlying epidemiologic associations between air pollution and morbidity, we explored changes in gene expression in humans following inhalation of fresh diesel exhaust (DE), a model for particulate air pollution. Methods: 14 ethnically homogeneous (white males), young, healthy subjects underwent sixty minute inhalation exposures on 2 separate days with clean air (CA) or freshly generated and diluted DE at a concentration of 300 Î¼g/m3 PM2.5. Prior to and 24 hours following each session, whole blood was sampled and fractionated for PBMC isolation, RNA extraction, and generation of cDNA, followed by hybridizationÂ withÂ Agilent Whole Human Genome (4X44K) arrays. Results: Oxidative stress and the ubiquitin proteasome pathway, as well as the coagulation system, were among hypothesized pathways identified by analysis of differentially expressed genes. Nine genes from these pathways were validated using real-time PCR comparing fold change in expression between DE exposed and clean (CA) days. Quantitative gene fold changes generated by real-time PCR were consistent with the directional fold changes from the microarray analysis. Conclusions: Changes in gene expression connected with key oxidative stress, protein degradation, and coagulation pathways are likely to underlie observed physiologic and clinical outcomes and suggest specific avenues and sensitive time points for further physiologic exploration. Diesel exhaust inhalation exposure-induced human gene expression changes were measured in peripheral blood mononuclear cells. 14 white males subjects were seated in a controlled environment facility for 2 separate 60 minute inhalation exposures which occurred at least 1 week apart to either clean air and freshly generate or diluted diesel exhaust (300ug/m3 PM2.5) .Blood collection occurred immediately prior to and 24 hours following exposures. Two microarrays per subject were completed using Agilent Whole Human Genome (4X44K) arrays. Genes that were of interest to our research group were verified using Real Time PCR analysis.

Dataset Information

Placental DNA methylation gene networks correlate with wildfire-informed particulate matter exposure and child neurodevelopment outcomes.

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets