{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T21:20:21Z","timestamp":1793136021843,"version":"4.5.0"},"posted":{"date-parts":[[2026,6,2]]},"group-title":"Developmental Biology","reference-count":35,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Karakin Foundation"},{"name":"Men of Distinction Award"},{"name":"Great Ormond Street Hospital for Sick Children's Charity"},{"name":"Funai Overseas Scholarship"},{"award":["10006049"],"award-info":[{"award-number":["10006049"]}],"id":[{"id":"https:\/\/ror.org\/03xk7zy09","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,2]]},"abstract":"<jats:title>STRUCTURED ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To characterize intestinal transcriptional profiles in gastroschisis, their temporal evolution, and response to fetal intervention.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Summary Background Data<\/jats:title>\n                  <jats:p>Gastroschisis causes significant intestinal dysfunction, with intra-abdominal bowel dilation clinically shown to correlate with worse outcomes. While inflammation and neurovascular impairment have been implicated, genome-wide transcriptional characterization of disease severity remains lacking.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    Using a fetal ovine model of complex gastroschisis, in which all gastroschisis animals demonstrated significant intra-abdominal bowel dilation at term, bulk RNA sequencing was performed on proximal small intestinal tissue from mid-gestation and term fetuses across three groups: normal, gastroschisis, and prenatally repaired gastroschisis. Differential gene expression (FDR \u2264 .05, |log\n                    <jats:sub>2<\/jats:sub>\n                    fold change| \u2265 1.5) and pathway enrichment analyses were performed, with targeted interrogation of extracellular matrix (ECM), enteric nervous system (ENS), angiogenic, and inflammatory pathways.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>At mid-gestation, gastroschisis intestine showed minimal transcriptional differences (150 differentially expressed genes [DEGs]) and some bowel dilation. By term, dysregulation was substantial (2,423 DEGs) alongside significant dilation. Normal ontogenetic intestinal maturation patterns were altered, with fewer expected developmental gene changes and discordant pathway regulation. ECM pathway aberrations emerged early and persisted, while ENS, angiogenic, and inflammatory pathways were only dysregulated at term. Fetal repair was associated with normalization of gene expression at term (29 DEGs vs controls).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Intestinal transcriptional changes in experimental gastroschisis parallel progressive bowel dilation, consistent with a mechanical stress contribution to intestinal injury. Prenatal repair normalizes both dilation and gene expression, indicating a dynamic and potentially modifiable transcriptional program that supports the rationale for early fetal intervention.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Mini Abstract<\/jats:title>\n                  <jats:p>In a fetal ovine model, progressive bowel dilation in gastroschisis parallels transcriptomic dysregulation of ECM remodeling, neurovascular impairment, and inflammation which is normalized by prenatal repair.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.29.728798","type":"posted-content","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T21:20:16Z","timestamp":1780435216000},"source":"Crossref","is-referenced-by-count":1,"title":["Intra-Abdominal Bowel Dilation in Experimental Gastroschisis is Associated with a Modifiable Transcriptomic Program of Intestinal Dysfunction"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6451-8867","authenticated-orcid":false,"given":"Mary Elizabeth","family":"Guerra","sequence":"first","affiliation":[{"name":"Department of Surgery, Division of Pediatric Surgery, Baylor College of Medicine and Texas Children\u2019s Hospital, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Arai","sequence":"additional","affiliation":[{"name":"My FetUZ Fetal Research Center, Department of Development and Regeneration, Cluster Woman and Child, Biomedical Sciences, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Joyeux","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Pediatric Surgery, Baylor College of Medicine and Texas Children\u2019s Hospital, Houston, TX, USA"},{"name":"My FetUZ Fetal Research Center, Department of Development and Regeneration, Cluster Woman and Child, Biomedical Sciences, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey C.","family":"Baxter","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Pediatric Surgery, Baylor College of Medicine and Texas Children\u2019s Hospital, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sourav","family":"Bose","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Pediatric Surgery, Baylor College of Medicine and Texas Children\u2019s Hospital, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyanth","family":"Thevasagayampillai","sequence":"additional","affiliation":[{"name":"Maternal and Fetal Medicine Division, Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 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