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PreprintPublic domainmedRxiv

Impact of air pollution and tobacco smoke on the placental small non-coding RNA landscape

8 more authors
  1. 1ISGlobal, Barcelona, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain; Barcelona InTerdisciplinary research gr

Abstract

Fetal development is highly sensitive to environmental influences, including maternal smoking during pregnancy (MSDP) and air pollution. The placenta may play a central role in mediating these effects through epigenetic mechanisms, including small non-coding RNAs (sncRNAs). While most studies have focused on microRNAs (miRNAs), other sncRNA classes remain poorly characterized. Here, we characterized the placental sncRNA landscape and investigated its associations with prenatal exposure to MSDP and air pollution. The sncRNA expression profile of 390 chorionic villi samples from the Barcelona Life Study Cohort (BiSC) was measured using small RNA sequencing and the seqBuster/seqCluster pipeline. MSDP was assessed via questionnaire, and prenatal exposure to black carbon (BC), particulate matter ≤2.5 μm (PM 2.5) , and nitrogen dioxide (NO 2) was estimated using hybrid dispersion-land-use regression (LUR) spatiotemporal models. Associations were evaluated using linear regressions adjusted for relevant covariates. We identified 979 placental sncRNA clusters, assigned primarily to miRNAs (33.2%), piRNAs (26.4%), snoRNAs (12.2%), tRFs (7.8%), and others (20.4%). MSDP was associated with the downregulation of miR-421 and the upregulation of multiple snoRNAs from the imprinted DLK1-DIO3 locus ( SNORD113-4, SNORD114-2, SNORD114-3, and SNORD114-17 ), as well as the piR-26394. No sncRNAs remained significantly associated with air pollution after multiple-testing correction, although several miRNAs showed suggestive associations. Overall, this study provides a comprehensive characterization of placental sncRNAs and identifies previously unreported smoking-associated sncRNAs within the imprinted DLK1-DIO3 locus, expanding our understanding of placental epigenetic responses to prenatal environmental exposures.

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BibTeX
@misc{falcongracia2026impact,
  title = {{Impact of air pollution and tobacco smoke on the placental small non-coding RNA landscape}},
  author = {A. Falcon-Gracia and H. Vespalcova and D. Peligri and S. Aguilar-Lacasana and L. Pantano and R. N. Nurtdinov and Z. Garcia and A. Dominguez and L. Gomez-Herrera and O. Sanchez and M. Gascon and M. Foraster and R. Guigo and E. Llurba and M. D. Gomez-Roig and I. Rivas and P. Dadvand and J. Sunyer and M. Bustamante and M. Cosin-Tomas},
  howpublished = {medRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.16.26365732},
  url = {https://www.medrxiv.org/content/10.64898/2026.10.16.26365732v1},
  note = {Public domain},
}
RIS
TY  - UNPB
TI  - Impact of air pollution and tobacco smoke on the placental small non-coding RNA landscape
AU  - A. Falcon-Gracia
AU  - H. Vespalcova
AU  - D. Peligri
AU  - S. Aguilar-Lacasana
AU  - L. Pantano
AU  - R. N. Nurtdinov
AU  - Z. Garcia
AU  - A. Dominguez
AU  - L. Gomez-Herrera
AU  - O. Sanchez
AU  - M. Gascon
AU  - M. Foraster
AU  - R. Guigo
AU  - E. Llurba
AU  - M. D. Gomez-Roig
AU  - I. Rivas
AU  - P. Dadvand
AU  - J. Sunyer
AU  - M. Bustamante
AU  - M. Cosin-Tomas
PY  - 2026
DA  - 2026/10/16
PB  - medRxiv
DO  - 10.64898/2026.10.16.26365732
UR  - https://www.medrxiv.org/content/10.64898/2026.10.16.26365732v1
AB  - Fetal development is highly sensitive to environmental influences, including maternal smoking during pregnancy (MSDP) and air pollution. The placenta may play a central role in mediating these effects through epigenetic mechanisms, including small non-coding RNAs (sncRNAs). While most studies have focused on microRNAs (miRNAs), other sncRNA classes remain poorly characterized. Here, we characterized the placental sncRNA landscape and investigated its associations with prenatal exposure to MSDP and air pollution. The sncRNA expression profile of 390 chorionic villi samples from the Barcelona Life Study Cohort (BiSC) was measured using small RNA sequencing and the seqBuster/seqCluster pipeline. MSDP was assessed via questionnaire, and prenatal exposure to black carbon (BC), particulate matter ≤2.5 μm (PM 2.5) , and nitrogen dioxide (NO 2) was estimated using hybrid dispersion-land-use regression (LUR) spatiotemporal models. Associations were evaluated using linear regressions adjusted for relevant covariates. We identified 979 placental sncRNA clusters, assigned primarily to miRNAs (33.2%), piRNAs (26.4%), snoRNAs (12.2%), tRFs (7.8%), and others (20.4%). MSDP was associated with the downregulation of miR-421 and the upregulation of multiple snoRNAs from the imprinted DLK1-DIO3 locus ( SNORD113-4, SNORD114-2, SNORD114-3, and SNORD114-17 ), as well as the piR-26394. No sncRNAs remained significantly associated with air pollution after multiple-testing correction, although several miRNAs showed suggestive associations. Overall, this study provides a comprehensive characterization of placental sncRNAs and identifies previously unreported smoking-associated sncRNAs within the imprinted DLK1-DIO3 locus, expanding our understanding of placental epigenetic responses to prenatal environmental exposures.
ER  -