{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T12:17:53Z","timestamp":1782821873692,"version":"3.54.5"},"reference-count":49,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T00:00:00Z","timestamp":1751673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Previous research has linked both endothelial protein changes and vitamin D with infertility. This study was undertaken to investigate the association of proteins associated with endothelial function and vitamin D status in the luteal phase at day 21 in a group of non-obese women prior to in vitro fertilization (IVF) with either unexplained infertility (UI) or male factor infertility (MFI). Twenty-five non-obese Caucasian women from a UK academic center with MFI (n = 14) and UI (n = 11) were recruited. Blood was withdrawn at day 21 of the menstrual cycle at the time of mock embryo transfer. Vitamin D parameters were measured by tandem mass spectroscopy. Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was undertaken for 20 protein markers of endothelial dysfunction. Baseline demographics did not differ between groups and parameters of response following IVF did not differ. Vitamins D2 and D3, and 1,25 Vitamin D3 did not differ between groups. In UI, markers of endothelial activation\/dysfunction were investigated; vascular cell adhesion molecule 1 (VCAM-1) decreased and this is associated with endothelial stress; vascular endothelial growth factor (VEGF) decreased and this may suggest impaired endometrial angiogenesis; while intercellular adhesion molecule 1 (ICAM-3) increased (p &lt; 0.05) and is associated with increased immunological activity. A marker of vascular integrity, angiopoietin-1, increased while soluble angiopoietin-1 receptor (sTie-2) decreased (p &lt; 0.05), suggesting increased vascular development. Endothelial markers of inflammation, coagulation, and endothelial progenitor cells were unchanged. Vitamin D and its metabolites show no relationship to UI, but endothelial activation\/dysfunction and vascular integrity changes in VCAM-1, VEGF, sICAM-3, angiopoietin-1, and sTie-2 may contribute to UI, though the mechanisms through which they work require further evaluation; however, these protein changes have been associated with endometriosis, raising the suggestion that subclinical\/undiagnosed endometriosis may have contributed to UI in these subjects.<\/jats:p>","DOI":"10.3390\/ijms26136485","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T08:58:23Z","timestamp":1751878703000},"page":"6485","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Endothelial Protein Changes Indicative of Endometriosis in Unexplained Infertility, an Exploratory Study"],"prefix":"10.3390","volume":"26","author":[{"given":"Heba","family":"Malik","sequence":"first","affiliation":[{"name":"School of Medicine, Royal College of Surgeons in Ireland-Medical University of Bahrain, Busaiteen P.O. Box 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8458-2710","authenticated-orcid":false,"given":"Sirine","family":"Zamouri","sequence":"additional","affiliation":[{"name":"School of Medicine, Royal College of Surgeons in Ireland-Medical University of Bahrain, Busaiteen P.O. Box 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Akkawi","sequence":"additional","affiliation":[{"name":"School of Medicine, Royal College of Surgeons in Ireland-Medical University of Bahrain, Busaiteen P.O. Box 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddh","family":"Mehra","sequence":"additional","affiliation":[{"name":"School of Medicine, Royal College of Surgeons in Ireland-Medical University of Bahrain, Busaiteen P.O. Box 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana","family":"Mouaki","sequence":"additional","affiliation":[{"name":"School of Medicine, Royal College of Surgeons in Ireland-Medical University of Bahrain, Busaiteen P.O. Box 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3544-2231","authenticated-orcid":false,"given":"Thozhukat","family":"Sathyapalan","sequence":"additional","affiliation":[{"name":"Hull York Medical School, University of Hull, Hull HU6 7RX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjula","family":"Nandakumar","sequence":"additional","affiliation":[{"name":"Research Department, Royal College of Surgeons in Ireland-Medical University of Bahrain, Busaiteen P.O. Box 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5762-3917","authenticated-orcid":false,"given":"Alexandra E.","family":"Butler","sequence":"additional","affiliation":[{"name":"Research Department, Royal College of Surgeons in Ireland-Medical University of Bahrain, Busaiteen P.O. Box 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5887-7257","authenticated-orcid":false,"given":"Stephen L.","family":"Atkin","sequence":"additional","affiliation":[{"name":"Research Department, Royal College of Surgeons in Ireland-Medical University of Bahrain, Busaiteen P.O. Box 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.clinbiochem.2018.03.012","article-title":"Fertility and infertility: Definition and epidemiology","volume":"62","author":"Wyns","year":"2018","journal-title":"Clin. Biochem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.fertnstert.2024.01.013","article-title":"Depression, anxiety, quality of life, and infertility: A global lens on the last decade of research","volume":"121","author":"Braverman","year":"2024","journal-title":"Fertil. Steril."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/s41585-018-0003-3","article-title":"Genetics of male infertility","volume":"15","author":"Krausz","year":"2018","journal-title":"Nat. Rev. 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