{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T15:03:57Z","timestamp":1784300637880,"version":"3.55.0"},"reference-count":63,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background\/Objectives<\/jats:title>\n                    <jats:p>Congenital diaphragmatic hernia (CDH) is a severe developmental anomaly with high etiological heterogeneity. Although numerous susceptibility genes have been identified, genetic factors alone fail to explain the full disease risk. Epidemiological data highlight the contribution of environmental exposures. Epigenetic regulation provides a crucial link bridging genetic predisposition and environmental influence. This review aims to summarize recent multiomics evidence elucidating how epigenetic mechanisms mediate gene\u2013environment interactions in CDH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This narrative review summarizes studies published over the past decade on epigenetic mechanisms in congenital diaphragmatic hernia (CDH), including DNA methylation, histone modifications, noncoding RNAs, and integrative genomic and transcriptomic analyses in human samples, animal models, and iPSC\u2010derived organoids. Relevant literature was identified through targeted searches of the biomedical literature and screening of reference lists from key articles. Relevant studies were considered according to their relevance to epigenetic regulation, gene\u2013environment interactions, and translational implications in CDH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Aberrant DNA methylation, histone acetylation imbalance, and dysregulated miRNAs converge on key developmental pathways, including retinoic acid, TGF\u2010\u03b2, and NF\u2010\u03baB signaling. Experimental evidence shows that miR\u2010200b supplementation or pharmacological restoration of histone acetylation can partially rescue pulmonary hypoplasia in nitrofen\u2010induced CDH models. iPSC and organoid systems further demonstrate synergistic effects between genetic susceptibility and mechanical stress, supporting epigenetic regulation as a mechanistic bridge.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Epigenetic mechanisms serve as core mediators linking genetic and environmental factors in CDH pathogenesis. Future directions include large\u2010scale EWAS\/WGBS and multiomics integration, establishment of standardized epigenetic databases, and ethically guided development of prenatal epigenetic diagnostics and targeted interventions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bdr2.70047","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T09:51:16Z","timestamp":1778665876000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["How Epigenetics Bridges Genes and Environment: A Multiomics Evidence Chain in Congenital Diaphragmatic Hernia"],"prefix":"10.1002","volume":"118","author":[{"given":"Yunshan","family":"Gao","sequence":"first","affiliation":[{"name":"Kunming Children's Hospital  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Zhu","sequence":"additional","affiliation":[{"name":"Kunming Children's Hospital  Kunming 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