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However, a clear interconnection between placenta metabolism, succinate levels, SUCNR1 signalling and pregnancy pathologies remains elusive. Here, we set out to investigate the potential role of succinate on labour and placental mechanisms by combining clinical and functional experimental data at the same time as exploring the specific SUCNR1\u2010mediated effects of succinate on placenta vascularization, addressing its specific agonist actions. According to our data, succinate levels vary throughout pregnancy and postpartum, with a natural increase during the peripartum period. We also show that SUCNR1 activation in the umbilical cord endothelium promotes angiogenesis under normal conditions. However, in GDM, excessive succinate and impaired SUCNR1 function may weaken this angiogenic response. In conclusion, the present study underlines succinate as an emerging signalling molecule in the placenta, regulating labour and placental processes. The reduced sensitivity of the succinate\/SUCNR1 pathway in the GDM environment may serve as a protective physiological mechanism or could have a pathogenic effect.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n Succinate levels increase at delivery in maternal and fetal circulation.<\/jats:p>\n <\/jats:list-item>\n \n Gestational diabetes (GDM) induces succinate accumulation and SUCNR1 downregulation in umbilical cords.<\/jats:p>\n <\/jats:list-item>\n \n GDM compromises angiogenic gene profile modulation by SUCNR1 in umbilical cord endothelium.<\/jats:p>\n <\/jats:list-item>\n \n SUCNR1 activation stimulates sprouting and tube\u2010forming capacity of human umbilical vein endothelial cells from healthy, but not GDM pregnancies.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp288010","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T16:01:16Z","timestamp":1743523276000},"page":"4261-4278","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Impaired angiogenesis in gestational diabetes is linked to succinate\/SUCNR1 axis dysregulation in late gestation"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7006-9925","authenticated-orcid":false,"given":"Sergiy","family":"Klid","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery Rovira i Virgili University Tarragona Spain"},{"name":"CIBER de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM) Instituto de Salud Carlos III Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Algaba\u2010Chueca","sequence":"additional","affiliation":[{"name":"CIBER de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM) Instituto de Salud Carlos III Madrid Spain"},{"name":"Department of Endocrinology and Nutrition, Research Unit University Hospital of Tarragona Joan XXIII\u2010Institut d'Investigaci\u00f3 Sanit\u00e0ria Pere Virgili (IISPV) Tarragona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9133-3120","authenticated-orcid":false,"given":"Elsa","family":"Maym\u00f3\u2010Masip","sequence":"additional","affiliation":[{"name":"CIBER de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM) Instituto de Salud Carlos III Madrid Spain"},{"name":"Department of Endocrinology and Nutrition, Research Unit University Hospital of Tarragona Joan XXIII\u2010Institut d'Investigaci\u00f3 Sanit\u00e0ria Pere Virgili (IISPV) Tarragona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Ballesteros","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery Rovira i Virgili University Tarragona Spain"},{"name":"CIBER de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM) Instituto de Salud Carlos III Madrid Spain"},{"name":"Department of Obstetrics and Gynecology University Hospital of Tarragona Joan XXIII. 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