{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T01:47:14Z","timestamp":1789264034526,"version":"build-2803163510"},"reference-count":84,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T00:00:00Z","timestamp":1616025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007172","name":"Cincinnati Children's Hospital Medical Center","doi-asserted-by":"publisher","award":["Internal Funding"],"award-info":[{"award-number":["Internal Funding"]}],"id":[{"id":"10.13039\/100007172","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Congenital diaphragmatic hernia (CDH) is characterized by the herniation of abdominal contents into the thoracic cavity during the fetal period. This competition for fetal thoracic space results in lung hypoplasia and vascular maldevelopment that can generate severe pulmonary hypertension (PH). The detailed mechanisms of CDH pathogenesis are yet to be understood. Acknowledgment of the lung metabolism during the in-utero CDH development can help to discern the CDH pathophysiology changes. Timed-pregnant dams received nitrofen or vehicle (olive oil) on E9.5 day of gestation. All fetal lungs exposed to nitrofen or vehicle control were harvested at day E21.5 by C-section and processed for metabolomics analysis using nuclear magnetic resonance (NMR) spectroscopy. The three groups analyzed were nitrofen-CDH (NCDH), nitrofen-control (NC), and vehicle control (VC). A total of 64 metabolites were quantified and subjected to statistical analysis. The multivariate analysis identified forty-four metabolites that were statistically different between the three groups. The highest Variable importance in projection (VIP) score (&gt;2) metabolites were lactate, glutamate, and adenosine 5\u2032-triphosphate (ATP). Fetal CDH lungs have changes related to oxidative stress, nucleotide synthesis, amino acid metabolism, glycerophospholipid metabolism, and glucose metabolism. This work provides new insights into the molecular mechanisms behind the CDH pathophysiology and can explore potential novel treatment targets for CDH patients.<\/jats:p>","DOI":"10.3390\/metabo11030177","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T11:41:06Z","timestamp":1616067666000},"page":"177","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Lung Metabolomics Profiling of Congenital Diaphragmatic Hernia in Fetal Rats"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5890-7786","authenticated-orcid":false,"given":"Maria del Mar","family":"Romero-Lopez","sequence":"first","affiliation":[{"name":"Center for Fetal and Placental Research, Division of Pediatric General and Thoracic Surgery, Cincinnati Children\u2019s Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA"},{"name":"Perinatal Institute, Division of Neonatology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9132-9271","authenticated-orcid":false,"given":"Marc","family":"Oria","sequence":"additional","affiliation":[{"name":"Center for Fetal and Placental Research, Division of Pediatric General and Thoracic Surgery, Cincinnati Children\u2019s Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA"},{"name":"Department of Surgery, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Watanabe-Chailland","sequence":"additional","affiliation":[{"name":"NMR-based Metabolomics Core, Division of Pathology and Laboratory Medicine, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Florencia","family":"Varela","sequence":"additional","affiliation":[{"name":"Center for Fetal and Placental Research, Division of Pediatric General and Thoracic Surgery, Cincinnati Children\u2019s Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey","family":"Romick-Rosendale","sequence":"additional","affiliation":[{"name":"NMR-based Metabolomics Core, Division of Pathology and Laboratory Medicine, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose L.","family":"Peiro","sequence":"additional","affiliation":[{"name":"Center for Fetal and Placental Research, Division of Pediatric General and Thoracic Surgery, Cincinnati Children\u2019s Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA"},{"name":"Department of Surgery, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1053\/j.sempedsurg.2017.04.008","article-title":"Congenital diaphragmatic hernia-associated pulmonary hypertension","volume":"26","author":"Harting","year":"2017","journal-title":"Semin. 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