{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T18:27:24Z","timestamp":1784917644045,"version":"3.55.0"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T00:00:00Z","timestamp":1671580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Women with polycystic ovary syndrome (PCOS) exhibit complement factor expression changes that may be obesity-driven rather than an intrinsic facet of PCOS; furthermore, complement changes have been associated with vitamin D deficiency, a common feature of PCOS. Therefore, complement pathway proteins and vitamin D levels may be linked in PCOS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We measured plasma levels of complement pathway proteins by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement for the classical (C4, C4a, and C4b) and alternative pathways (C3, C3b, iC3b, properdin, and factors B, D, and H) in weight and age-matched non-obese non-insulin resistant women with PCOS (n = 24) and control women (n = 24). Proteins that differed between groups were correlated with 25-hydroxyvitamin D<jats:sub>3<\/jats:sub> (25(OH)D<jats:sub>3<\/jats:sub>) and 1,25-dihydroxyvitamin D<jats:sub>3<\/jats:sub> (1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>), measured by isotope-dilution liquid chromatography tandem mass spectrometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Women with PCOS had a higher free androgen index and anti-Mullerian hormone, though insulin resistance was comparable to controls; likewise, C-reactive protein, a marker of inflammation, was comparable between cohorts. In the alternative complement pathway, C3, iC3b, and properdin were increased in PCOS (p &amp;lt;0.05), while C4 in the classical pathway was increased (p &amp;lt;0.05). 25(OH)D<jats:sub>3<\/jats:sub> levels positively correlated with C3b only in control subjects, with no correlation of 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> with any of the proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In a non-obese PCOS population matched for age, insulin resistance and inflammation, initiating proteins of the classical and alternate complement cascades were increased. However, a positive correlation with 25(OH)D<jats:sub>3<\/jats:sub> was only seen for C3b in control subjects, with no correlation to 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>, suggesting that the increase in complement proteins in PCOS is vitamin D-independent.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.935750","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T06:33:47Z","timestamp":1671604427000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Classical and alternate complement factor overexpression in non-obese weight matched women with polycystic ovary syndrome does not correlate with vitamin D"],"prefix":"10.3389","volume":"13","author":[{"given":"Abu Saleh Md","family":"Moin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thozhukat","family":"Sathyapalan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra E.","family":"Butler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen L.","family":"Atkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-11-0755","article-title":"Recent advances in cardiovascular aspects of polycystic ovary syndrome","volume":"166","author":"Sathyapalan","year":"2012","journal-title":"Eur J Endocrinol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.6064\/2012\/402783","article-title":"Complement activation: An emerging player in the pathogenesis of cardiovascular disease","volume":"2012","author":"Carter","year":"2012","journal-title":"Scientifica"},{"key":"B3","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1111\/cen.14322","article-title":"Complement activation in polycystic ovary syndrome occurs in the postprandial and fasted state and is influenced by obesity and insulin sensitivity","volume":"94","author":"Lewis","year":"2021","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2011.01.136","article-title":"Serum complement C3 has a stronger association with insulin resistance than high-sensitivity c-reactive protein in women with polycystic ovary syndrome","volume":"95","author":"Yang","year":"2011","journal-title":"Fertil Steril"},{"key":"B5","article-title":"Assessment of c-reactive protein and C3 as inflammatory markers of insulin resistance in women with polycystic ovary syndrome: A case-control study","volume":"14","author":"Dehdashtihaghighat","year":"2013","journal-title":"J Reprod infertility"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1055\/s-2006-948308","article-title":"Low serum 25-hydroxyvitamin d concentrations are associated with insulin resistance and obesity in women with polycystic ovary syndrome","volume":"114","author":"Hahn","year":"2006","journal-title":"Exp Clin Endocrinol Diabetes"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2011.03.002","article-title":"Vitamin d deficiency is common and associated with metabolic risk factors in patients with polycystic ovary syndrome","volume":"60","author":"Li","year":"2011","journal-title":"Metabol: Clin Exp"},{"key":"B8","doi-asserted-by":"publisher","first-page":"105892","DOI":"10.1016\/j.jsbmb.2021.105892","article-title":"Vitamin d deficiency effects on cardiovascular parameters in women with polycystic ovary syndrome: A retrospective, cross-sectional study","volume":"211","author":"Butler","year":"2021","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-13-0617","article-title":"The role of vitamin d in metabolic disturbances in polycystic ovary syndrome (PCOS): A systematic review","volume":"169","author":"Krul-Poel","year":"2013","journal-title":"Eur J endocrinology\/European Fed Endoc Societies"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3177\/jnsv.63.155","article-title":"Vitamin d insufficiency predicts elevated levels of complement 3 independent of insulin resistance and BMI","volume":"63","author":"Ahmad","year":"2017","journal-title":"J Nutr Sci Vitaminol (Tokyo)"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00013","article-title":"Association of vitamin d metabolites with embryo development and fertilization in women with and without PCOS undergoing subfertility treatment","volume":"10","author":"Cunningham","year":"2019","journal-title":"Front Endocrinol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh098","article-title":". 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