{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T08:04:37Z","timestamp":1784880277635,"version":"3.55.0"},"reference-count":59,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Objective: Vitamin D has been reported to act as a tissue-protective regulator by suppressing Matrix Metalloproteinases (MMPs) and upregulating Tissue Inhibitors of Metalloproteinases (TIMPs), though changes may be body mass index (BMI)-dependent; however, the relationship between vitamin D metabolism and matrix remodeling pathways in Polyendocrine Metabolic Ovarian Syndrome (PMOS) remains poorly understood. Methods: In women with PMOS (n = 28) and controls (n = 28), 12 MMPs and 3 TIMPs were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement and correlated to 25-hydroxyvitamin D3 (25(OH)D3) and its metabolites (active 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3)) measured by gold standard isotope-dilution liquid chromatography tandem mass spectrometry. Results: Insulin resistance and systemic inflammation (normal C-reactive protein) were comparable between PMOS and control women, though PMOS had higher free androgen index and anti-Mullerian hormone levels. Vitamin D and its metabolites did not differ between groups. Only MMP16 was lower in PMOS than controls (549.6 \u00b1 58.3 vs. 678.0 \u00b1 304.1 Relative Fluorescent Units, p = 0.037) but did not pass the false discovery rate. In women with PMOS, 25(OH)D3 and 24,25(OH)2D3 demonstrated significant inverse correlations with TIMP3 (r = \u22120.60, p = 0.005 and r = \u22120.58, p = 0.007, respectively). Multivariable regression confirmed independent inverse associations between TIMP3 and both 25(OH)D3 (\u03b2 = \u221251.1, p = 0.031) and 24,25(OH)2D3 (\u03b2 = \u2212858.7, p = 0.028) after adjustment for age, body mass index and Homeostatic Model Assessment-Insulin Resistance, and the association remained stable following bootstrap internal validation. Additional moderate associations were observed between vitamin D metabolites and membrane-type MMPs (MMP14, MMP16, MMP17). Conclusions: Exploratory analyses suggested potential inverse associations between vitamin D metabolites and TIMP3, together with weaker associations involving MMP14, MMP16 and MMP17, suggesting the novel hypothesis that vitamin D may influence extracellular matrix remodeling and ovarian stromal biology through regulation of TIMP3-dependent pathways independently of obesity and insulin resistance, rather than through MMPs directly.<\/jats:p>","DOI":"10.3390\/ph19081144","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T07:36:13Z","timestamp":1784878573000},"page":"1144","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Exploratory Study of Vitamin D and Matrix Metalloproteinase and Their Regulators in Polyendocrine Metabolic Ovarian Syndrome"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1352-7912","authenticated-orcid":false,"given":"Mashael","family":"Zainalabedin","sequence":"first","affiliation":[{"name":"School of Medicine, Royal College of Surgeons in Ireland-Medical University of Bahrain, Busaiteen 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4723-7221","authenticated-orcid":false,"given":"Nora","family":"Smahi","sequence":"additional","affiliation":[{"name":"School of Medicine, Royal College of Surgeons in Ireland-Medical University of Bahrain, Busaiteen 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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5762-3917","authenticated-orcid":false,"given":"Alexandra E.","family":"Butler","sequence":"additional","affiliation":[{"name":"School of Medicine, Royal College of Surgeons in Ireland-Medical University of Bahrain, Busaiteen 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":"School of Medicine, Royal College of Surgeons in Ireland-Medical University of Bahrain, Busaiteen 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1016\/S0140-6736(26)00717-8","article-title":"Polyendocrine metabolic ovarian syndrome, the new name for polycystic ovary syndrome: A multistep global consensus process","volume":"407","author":"Teede","year":"2026","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4609","DOI":"10.1210\/jc.2007-1343","article-title":"Young obese women with polycystic ovary syndrome have evidence of early coronary atherosclerosis","volume":"92","author":"Shroff","year":"2007","journal-title":"J. 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