{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T19:57:28Z","timestamp":1781207848683,"version":"3.54.1"},"reference-count":45,"publisher":"American Diabetes Association","issue":"1","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/501100003483","name":"Hebrew University of Jerusalem","doi-asserted-by":"publisher","award":["TS & MS"],"award-info":[{"award-number":["TS & MS"]}],"id":[{"id":"10.13039\/501100003483","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Israeli Planning and Budgeting Committee"},{"name":"Kaplan Medical Center"},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["ISF 462\/22"],"award-info":[{"award-number":["ISF 462\/22"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Gestational diabetes mellitus (GDM) is defined as hyperglycemia first identified during pregnancy and can lead to adverse maternal and neonatal outcomes. The molecular mechanisms leading to these outcomes are currently poorly understood. While transcriptomics of GDM placentas has been previously studied, the effect on precursor mRNA splicing remains largely unknown. This study explores the impact of GDM on placental splicing and identifies its regulatory mechanisms. Using RNA sequencing data from Norwegian and Chinese cohorts, we uncovered thousands of differential splicing events. Pathway enrichment analysis revealed significant associations with metabolic and diabetes-related pathways. Splicing factor motif and cross-linking and immunoprecipitation sequencing analyses highlighted serine\/arginine-rich splicing factor 10 (SRSF10) as a key regulator in this process, with its binding enriched at misspliced exons. Silencing SRSF10 in placental cells mirrored GDM-associated missplicing in key genes. These findings underscore splicing dysregulation as a critical process in GDM pathogenesis, suggesting that targeting SRSF10 could be a potential therapeutic approach to mitigate the deleterious effects of GDM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>Gestational diabetes mellitus (GDM) causes hyperglycemia during pregnancy and adverse maternal and neonatal outcomes. Bulk placental gene expression has been reported largely unchanged. RNA sequencing of Norwegian and Chinese GDM placentas reveals hundreds of differential splicing events enriched for metabolic- and diabetes-related pathways. Motif enrichment and cross-linking and immunoprecipitation sequencing integration identify serine\/arginine splicing factor 10 as a key regulator of GDM-associated missplicing. Silencing serine\/arginine splicing factor 10 in placental models recapitulates the GDM-associated missplicing program.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db25-0333","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T17:01:58Z","timestamp":1763485318000},"page":"193-204","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":0,"title":["Gestational Diabetes Mellitus Alters Placental Precursor mRNA Splicing"],"prefix":"10.2337","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4353-6521","authenticated-orcid":false,"given":"Eden","family":"Engal","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, The Institute for Medical Research Israel\u2013Canada, Faculty of Medicine, The Hebrew University of Jerusalem 1 , Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6607-1820","authenticated-orcid":false,"given":"Adi","family":"Gershon","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, The Institute for Medical Research Israel\u2013Canada, Faculty of Medicine, The Hebrew University of Jerusalem 1 , Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiri","family":"Melamed","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, The Institute for Medical Research Israel\u2013Canada, Faculty of Medicine, The Hebrew University of Jerusalem 1 , Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2622-9386","authenticated-orcid":false,"given":"Aveksha","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, The Institute for Medical Research Israel\u2013Canada, Faculty of Medicine, The Hebrew University of Jerusalem 1 , Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadas","family":"Ner-Gaon","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Ben-Gurion University of the Negev 2 , Beer-Sheva, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2297-1055","authenticated-orcid":false,"given":"Shiri","family":"Jaffe-Herman","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, The Institute for Medical Research Israel\u2013Canada, Faculty of Medicine, The Hebrew University of Jerusalem 1 , Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuval","family":"Nevo","sequence":"additional","affiliation":[{"name":"Info-CORE, Bioinformatics Unit of the I-CORE Computation Center, The Hebrew University of Jerusalem 3 , Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0457-432X","authenticated-orcid":false,"given":"Alena","family":"Kirzhner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine A, Kaplan Medical Center and Faculty of Medicine, Hebrew University of Jerusalem 4 , Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oren","family":"Barak","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kaplan Medical Center and Faculty of Medicine, Hebrew University of Jerusalem 5 , Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edi","family":"Vaisbuch","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kaplan Medical Center and Faculty of Medicine, Hebrew University of Jerusalem 5 , Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian","family":"Kay","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, The Institute for Medical Research Israel\u2013Canada, Faculty of Medicine, The Hebrew University of Jerusalem 1 , Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Cathrine","family":"Staff","sequence":"additional","affiliation":[{"name":"Institute for Clinical Medicine, Faculty of Medicine, University of Oslo 6 , Oslo, Norway"},{"name":"Division of Obstetrics and Gynaecology, Oslo University Hospital 7 , Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Dechend","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center, a cooperation between the Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association and the Charit\u00e9 - Universit\u00e4tsmedizin Berlin 8 , Berlin, Germany"},{"name":"Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association (MDC) 9 , Berlin, Germany"},{"name":"Department of Cardiology and Nephrology 10 , Helios Clinic, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Herse","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center, a cooperation between the Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association and the Charit\u00e9 - Universit\u00e4tsmedizin Berlin 8 , Berlin, Germany"},{"name":"Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association (MDC) 9 , Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tal","family":"Shay","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Ben-Gurion University of the Negev 2 , Beer-Sheva, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8812-5577","authenticated-orcid":false,"given":"Maayan","family":"Salton","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, The Institute for Medical Research Israel\u2013Canada, Faculty of Medicine, The Hebrew University of Jerusalem 1 , Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8378-2903","authenticated-orcid":false,"given":"Tal","family":"Schiller","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Metabolism, Kaplan Medical Center and Faculty of Medicine, Hebrew University of Jerusalem 11 , Jerusalem, Israel"},{"name":"Department of Diabetes and Endocrinology, The Edith Wolfson Medical Center, affiliated to the Gray Faculty of Medical and Health Sciences, Tel Aviv University 12 , Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"2026061115275150800_B1","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.ajog.2021.08.006","article-title":"Further implications from a pragmatic randomized clinical trial of gestational diabetes screening: per-protocol and as-treated estimates","volume":"225","author":"Hillier","year":"2021","journal-title":"Am J Obstet Gynecol"},{"key":"2026061115275150800_B2","doi-asserted-by":"crossref","first-page":"e009494","DOI":"10.1136\/bmjopen-2015-009494","article-title":"A cohort study of trends in the prevalence of pregestational diabetes in pregnancy recorded in UK general practice between 1995 and 2012","volume":"6","author":"Coton","year":"2016","journal-title":"BMJ Open"},{"key":"2026061115275150800_B3","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.2337\/dci17-0045","article-title":"The human placenta in diabetes and obesity: friend or foe? the 2017 Norbert Freinkel award lecture","volume":"41","author":"Desoye","year":"2018","journal-title":"Diabetes Care"},{"key":"2026061115275150800_B4","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.15585\/mmwr.mm6743a2","article-title":"Prevalence and changes in preexisting diabetes and gestational diabetes among women who had a live birth - 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