{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T16:47:09Z","timestamp":1776271629749,"version":"3.50.1"},"posted":{"date-parts":[[2026,3,13]]},"group-title":"In Review","reference-count":46,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,6]]},"abstract":"<title>Abstract<\/title>\n                <p>Dysregulation of the airway epithelium contributes to recurrent wheezing and asthma and may have developmental origins. However, direct interrogation of fetal airway epithelium is not feasible, limiting investigation of prenatal epithelial programming. We performed high-throughput target-capture DNA methylation sequencing of matched amniotic epithelial biopsies and neonatal nasal brushings from 84 mother-infant pairs within the Airway Epithelium Respiratory Illnesses and Allergy (AERIAL) cohort. Tissue-specific methylation landscapes were compared to assess conservation and to explore associations with gestational exposures known to influence childhood asthma risk, including maternal asthma history and maternal prenatal smoking. We identified 4,897 differentially methylated regions between amniotic and nasal tissues (FDR \u2264 0.05 and log2FC \u2265 |0.2|), generally hypermethylated in the nasal epithelium. Despite differences, 1,493,976 CpG loci (~20%) revealed highly concordant methylation between tissues (FDR \u2265 0.1 and Pearson\u2019s R \u2265 0.8). Within this conserved methylome fraction, exposure-associated CpG sites were linked to maternal asthma history (55 CpGs) and prenatal smoking exposure (164 CpGs), with consistent directionality in both tissues. These analyses were exploratory and limited by small numbers of exposed participants. Amniotic epithelium shares conserved methylation features with neonatal nasal epithelium, supporting its utility as a surrogate for studying developmental programming of airway vulnerability and early asthma risk.<\/p>","DOI":"10.21203\/rs.3.rs-9050564\/v1","type":"posted-content","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T15:18:47Z","timestamp":1773415127000},"source":"Crossref","is-referenced-by-count":0,"title":["Programming of the respiratory epithelium in utero - insights from the amniotic epithelial methylome"],"prefix":"10.21203","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3703-4111","authenticated-orcid":false,"given":"Patricia","family":"Agudelo-Romero","sequence":"first","affiliation":[{"name":"The Kids Research Institute Australia"}]},{"given":"Thomas","family":"Iosifidis","sequence":"additional","affiliation":[{"name":"The Kids Research Institute Australia"}]},{"given":"James","family":"Lim","sequence":"additional","affiliation":[{"name":"The Kids Research Institute Australia"}]},{"given":"Nina","family":"Kresoje","sequence":"additional","affiliation":[{"name":"The Kids Research Institute Australia"}]},{"given":"David","family":"Hancock","sequence":"additional","affiliation":[{"name":"The Kids Research Institute Australia"}]},{"given":"David","family":"Hancock","sequence":"additional","affiliation":[{"name":"The Kids Research Institute Australia"}]},{"given":"Abhinav","family":"Sharma","sequence":"additional","affiliation":[{"name":"Stellenbosch University, Faculty of Medicine and Health Sciences"}]},{"given":"Talya","family":"Conradie","sequence":"additional","affiliation":[{"name":"The Kids Research Institute Australia"}]},{"given":"Minda","family":"Amin","sequence":"additional","affiliation":[{"name":"The Kids Research Institute Australia"}]},{"given":"Yuliya","family":"Karpievitch","sequence":"additional","affiliation":[{"name":"The Kids Research Institute Australia"}]},{"given":"Desiree","family":"Silva","sequence":"additional","affiliation":[{"name":"The Kids Research Institute Australia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4335-615X","authenticated-orcid":false,"given":"Anthony","family":"Bosco","sequence":"additional","affiliation":[{"name":"The University of Arizona"}]},{"given":"Susan","family":"Prescott","sequence":"additional","affiliation":[{"name":"The Kids Research Institute Australia"}]},{"given":"Peter","family":"LeSou\u00ebf","sequence":"additional","affiliation":[{"name":"The Kids Research Institute Australia"}]},{"given":"Elizabeth","family":"Kicic-Starcevich","sequence":"additional","affiliation":[{"name":"The Kids Research Institute Australia"}]},{"given":"Anthony","family":"Kicic","sequence":"additional","affiliation":[{"name":"UWA"}]},{"given":"David","family":"Martino","sequence":"additional","affiliation":[{"name":"The Kids Research Institute Australia"}]},{"given":"Stephen","family":"Stick","sequence":"additional","affiliation":[{"name":"Telethon Kids Institute, University of Western Australia"}]}],"member":"297","reference":[{"key":"ref1","doi-asserted-by":"crossref","DOI":"10.3389\/fmicb.2013.00391","article-title":"Epidemiology of virus-induced wheezing\/asthma in children","volume":"4","author":"Inoue Y","year":"2013","unstructured":"Inoue Y, Shimojo N (2013) Epidemiology of virus-induced wheezing\/asthma in children. 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