{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T14:28:38Z","timestamp":1770820118500,"version":"3.50.1"},"posted":{"date-parts":[[2025,10,3]]},"group-title":"Pediatrics","reference-count":41,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Dysregulation of the airway epithelium contributes to recurrent wheezing and asthma and may have developmental origins. Direct interrogation of fetal airway epithelium is not feasible in humans limiting investigation of prenatal epithelial programming.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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. We compared tissue-specific methylation landscapes for conservation and explored associations with gestational exposures known to influence childhood asthma risk (maternal asthma history and maternal prenatal smoking exposure).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Between amniotic and nasal tissues, we identified 4,897 differentially methylated regions (FDR \u2264 0.05 and log\n                    <jats:sub>2<\/jats:sub>\n                    FC \u2265 |0.2|) that were generally hypermethylated in the nasal epithelium. Despite these extensive tissue-specific differences, filtering for non-significant differential methylation loci (FDR \u2265 0.1) revealed 1,493,975 CpG loci (\u223c20%) with highly concordant methylation levels between tissues (Pearson\u2019s R &gt; 0.8). Within this conserved methylome fraction, we identified exposure-associated CpG sites linked to maternal asthma history (55 CpGs) and prenatal smoking exposure (164 CpGs) that showed consistent directionality in both tissues. These analyses were exploratory and limited by small numbers of exposed participants.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Amniotic epithelium shares a subset of conserved methylation features with the nasal epithelium, supporting its utility as a valuable surrogate for studying aspects of developmental programming of airway vulnerability. While exposure-associated signals were detectable within the conserved methylome fraction, these findings should be considered preliminary, but provide an encouraging framework for early risk stratification in asthma.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.10.02.25337047","type":"posted-content","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T15:05:18Z","timestamp":1759503918000},"source":"Crossref","is-referenced-by-count":0,"title":["Programming of the respiratory epithelium\n                  <i>in utero -<\/i>\n                  insights from the amniotic epithelial methylome"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3703-4111","authenticated-orcid":false,"given":"Patricia","family":"Agudelo-Romero","sequence":"first","affiliation":[{"name":"Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, Perth, 6009, Western Australia, Australia"},{"name":"School of Molecular Sciences, The University of Western Australia, Perth, Western Australia 6009, Australia"},{"name":"European Virus Bioinformatics Centre, Friedrich-Schiller-Universitat Jena, 07737 Jena, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8462-5865","authenticated-orcid":false,"given":"Thomas","family":"Iosifidis","sequence":"additional","affiliation":[{"name":"Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, Perth, 6009, Western Australia, Australia"},{"name":"School of Population Health, Curtin University, Perth, 6102, Western Australia, Australia"},{"name":"Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia, Perth, 6009, Western Australia, Australia"}]},{"given":"James","family":"Lim","sequence":"additional","affiliation":[{"name":"Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, Perth, 6009, Western Australia, Australia"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7104-3362","authenticated-orcid":false,"given":"Nina","family":"Kresoje","sequence":"additional","affiliation":[{"name":"Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, Perth, 6009, Western Australia, Australia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4782-2661","authenticated-orcid":false,"given":"David G.","family":"Hancock","sequence":"additional","affiliation":[{"name":"Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, Perth, 6009, Western Australia, Australia"},{"name":"Department of Respiratory and Sleep Medicine, Perth Children\u2019s Hospital Perth, Perth, 6009, Western Australia, Australia"},{"name":"Medical School, The University of Western Australia, Perth, 6009, Western Australia, Australia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9888-5385","authenticated-orcid":false,"given":"Guicheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, Perth, 6009, Western Australia, Australia"},{"name":"School of Population Health, Curtin University, Perth, 6102, Western Australia, Australia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6402-6993","authenticated-orcid":false,"given":"Abhinav","family":"Sharma","sequence":"additional","affiliation":[{"name":"DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, 7700, South Africa"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6380-5737","authenticated-orcid":false,"given":"Talya","family":"Conradie","sequence":"additional","affiliation":[{"name":"Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, Perth, 6009, Western Australia, Australia"}]},{"given":"Minda","family":"Amin","sequence":"additional","affiliation":[{"name":"Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, Perth, 6009, Western Australia, Australia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2586-3358","authenticated-orcid":false,"given":"Yuliya V.","family":"Karpievitch","sequence":"additional","affiliation":[{"name":"Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, Perth, 6009, Western Australia, Australia"},{"name":"School of Population Health, Curtin University, Perth, 6102, Western Australia, Australia"},{"name":"School of Biomedical Sciences, The University of Western Australia, Perth, 6009, Western Australia, Australia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4454-466X","authenticated-orcid":false,"given":"Desiree T.","family":"Silva","sequence":"additional","affiliation":[{"name":"Medical School, The University of Western Australia, Perth, 6009, Western Australia, Australia"},{"name":"The Kids Research Institute Australia, Perth, 6009, Western Australia, Australia"},{"name":"School of Medical and Health Sciences, Edith Cowan University, Perth, 6027, Western Australia, Australia"},{"name":"Department of Paediatrics and Neonatology, Joondalup Health Campus, Perth, 6027, Western Australia, Australia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4335-615X","authenticated-orcid":false,"given":"Anthony","family":"Bosco","sequence":"additional","affiliation":[{"name":"Asthma and Airway Disease Research Center University of Arizona, Tucson, 85721, Arizona, United States"},{"name":"Department of Immunobiology, The University of Arizona College of Medicine, Tucson, 85721, Arizona, United States"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4845-8590","authenticated-orcid":false,"given":"Susan L.","family":"Prescott","sequence":"additional","affiliation":[{"name":"Medical School, The University of Western Australia, Perth, 6009, Western Australia, Australia"},{"name":"The Kids Research Institute Australia, Perth, 6009, Western Australia, Australia"},{"name":"Nova Institute for Health, Baltimore, 21231, Maryland, United States"},{"name":"Department of Family and Community Medicine, University of Maryland, Baltimore, 21231, Maryland, United States"}]},{"given":"Peter N.","family":"LeSou\u00ebf","sequence":"additional","affiliation":[{"name":"Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, Perth, 6009, Western Australia, Australia"},{"name":"School of Paediatrics and Child Health, University of Western Australia, Perth, 6027, Western Australia, Australia"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9113-8939","authenticated-orcid":false,"given":"Elizabeth","family":"Kicic-Starcevich","sequence":"additional","affiliation":[{"name":"Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, Perth, 6009, Western Australia, 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