{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:01:42Z","timestamp":1791644502020,"version":"4.3.4"},"reference-count":49,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre","doi-asserted-by":"publisher","award":["2017\/27\/B\/NZ5\/02393"],"award-info":[{"award-number":["2017\/27\/B\/NZ5\/02393"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study explores the proteomic composition of follicular fluid (FF) from women undergoing oocyte retrieval for in vitro fertilisation (IVF), with a focus on the effects of polycystic ovary syndrome (PCOS). FF samples were collected from 74 patients, including 34 with PCOS and 40 oocyte donors. Proteomic profiling using machine learning identified significant differences in protein abundance between the PCOS and control groups. Of the 484 quantified proteins, 20 showed significantly altered levels in the PCOS group. Functional annotation and pathway enrichment analysis pointed to the involvement of protease inhibitors and immune-related proteins in the pathophysiology of PCOS, suggesting that inflammation and immune dysregulation may play a key role. Additionally, HDL assembly was identified as a significant pathway, with apolipoprotein-AI (APOA1) and alpha-2-macroglobulin (A2M) as the major proteins involved. Notably, myosin light polypeptide 6 was the most downregulated protein, showing the highest absolute fold change, and may serve as a novel independent biomarker for PCOS.<\/jats:p>","DOI":"10.3390\/ijms252111749","type":"journal-article","created":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T04:59:54Z","timestamp":1730437194000},"page":"11749","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Proteomic Analysis of Follicular Fluid in Polycystic Ovary Syndrome: Insights into Protein Composition and Metabolic Pathway Alterations"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4265-7353","authenticated-orcid":false,"given":"Janusz","family":"Przewocki","sequence":"first","affiliation":[{"name":"Institute of Mathematics, University of Gdansk, 80-308 Gda\u0144sk, Poland"},{"name":"iYoni App\u2014For Fertility Treatment, LifeBite, 10-763 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5522-3282","authenticated-orcid":false,"given":"Adam","family":"\u0141ukaszuk","sequence":"additional","affiliation":[{"name":"Edinburgh Medical School, College of Medicine and Veterinary Medicine, The University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6094-2273","authenticated-orcid":false,"given":"Grzegorz","family":"Jakiel","sequence":"additional","affiliation":[{"name":"Invicta Research and Development Center, 81-740 Sopot, Poland"},{"name":"First Department of Obstetrics and Gynaecology, Centre of Postgraduate Medical Education, 01-004 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1270-3438","authenticated-orcid":false,"given":"Izabela","family":"Woc\u0142awek-Potocka","sequence":"additional","affiliation":[{"name":"Department of Gamete and Embryo Biology, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"K\u0142osi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Oncological Gynecology and Gynecological Endocrinology, Medical University of Gdansk, 80-214 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3327-6447","authenticated-orcid":false,"given":"Jolanta","family":"Olszewska","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nursing, Medical University of Gda\u0144sk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5996-6991","authenticated-orcid":false,"given":"Krzysztof","family":"\u0141ukaszuk","sequence":"additional","affiliation":[{"name":"iYoni App\u2014For Fertility Treatment, LifeBite, 10-763 Olsztyn, Poland"},{"name":"Department of Obstetrics and Gynecology Nursing, Medical University of Gda\u0144sk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1477-7827-7-40","article-title":"Follicular fluid content and oocyte quality: From single biochemical markers to metabolomics","volume":"7","author":"Revelli","year":"2009","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Brinca, A.T., Ramalhinho, A.C., Sousa, \u00c2., Oliani, A.H., Breitenfeld, L., Passarinha, L.A., and Gallardo, E. (2022). Follicular fluid: A powerful tool for the understanding and diagnosis of polycystic ovary syndrome. Biomedicines, 10.","DOI":"10.3390\/biomedicines10061254"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"10952","DOI":"10.18632\/aging.102497","article-title":"Global, regional, and national prevalence and disability-adjusted life-years for infertility in 195 countries and territories, 1990\u20132017: Results from a global burden of disease study, 2017","volume":"11","author":"Sun","year":"2019","journal-title":"Aging"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1093\/humupd\/dmr040","article-title":"Demographic and medical consequences of the postponement of parenthood","volume":"18","author":"Schmidt","year":"2012","journal-title":"Hum. Reprod. Update"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.srhc.2015.01.002","article-title":"Women\u2019s attitudes towards fertility and childbearing\u2014A study based on a national sample of Swedish women validating the Attitudes to Fertility and Childbearing Scale (AFCS)","volume":"6","author":"Soederberg","year":"2015","journal-title":"Sex. Reprod. Healthc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1210\/er.2011-1034","article-title":"Insulin resistance and the polycystic ovary syndrome revisited: An update on mechanisms and implications","volume":"33","author":"Dunaif","year":"2012","journal-title":"Endocr. Rev."},{"key":"ref_7","unstructured":"Firmansyah, A., Chalid, M.T., Farid, R.B., and Nusratuddin, N. (2018). The correlation between insulin-like growth factor binding protein 1 (IGFBP-1) and homeostasis model assessment of insulin resistance (HOMA-IR) in polycystic ovarian syndrome with insulin resistance. Int. J. Reprod. Biomed., 16."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"101561","DOI":"10.1016\/j.ghir.2023.101561","article-title":"Insulin-like growth factor (IGF) performance in ovarian function and applications in reproductive biotechnologies","volume":"72\u201373","author":"Piau","year":"2023","journal-title":"Growth Horm. IGF Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1093\/humupd\/dmq032","article-title":"Extra-and intra-ovarian factors in polycystic ovary syndrome: Impact on oocyte maturation and embryo developmental competence","volume":"17","author":"Qiao","year":"2011","journal-title":"Hum. Reprod. Update"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1071\/RD11904","article-title":"The impact of obesity on oocytes: Evidence for lipotoxicity mechanisms","volume":"24","author":"Wu","year":"2011","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1159\/000270900","article-title":"Effect of follicular fluid oxidative stress on meiotic spindle formation in infertile women with polycystic ovarian syndrome","volume":"69","author":"Chattopadhayay","year":"2010","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1210\/clinem\/dgac281","article-title":"Elevated levels of follicular fatty acids induce ovarian inflammation via ERK1\/2 and inflammasome activation in PCOS","volume":"107","author":"Lai","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.ejogrb.2021.02.023","article-title":"In vitro fertilization outcomes in women with polycystic ovary syndrome: A meta-analysis","volume":"259","author":"Tang","year":"2021","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1198\/016214507000000950","article-title":"Robust linear model selection based on least angle regression","volume":"102","author":"Khan","year":"2007","journal-title":"J. Am. Stat. Assoc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/pro.4218","article-title":"PANTHER: Making genome-scale phylogenetics accessible to all","volume":"31","author":"Thomas","year":"2022","journal-title":"Protein Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"D672","DOI":"10.1093\/nar\/gkad1025","article-title":"The reactome pathway knowledgebase 2024","volume":"52","author":"Milacic","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: Protein\u2013protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Rudnicka, E., Suchta, K., Grymowicz, M., Calik-Ksepka, A., Smolarczyk, K., Duszewska, A.M., Smolarczyk, R., and Meczekalski, B. (2021). Chronic low grade inflammation in pathogenesis of PCOS. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073789"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Almaeen, A.H., Alduraywish, A.A., Nabi, M., Shah, N.N., Shaik, R., and Tantry, B.A. (2022). Quantitative changes in white blood cells: Correlation with the hallmarks of polycystic ovary syndrome. Medicina, 58.","DOI":"10.3390\/medicina58040535"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Deraison, C., Bonnart, C., and Vergnolle, N. (2017). Proteases. Inflammation: From Molecular and Cellular Mechanisms to the Clinic, Wiley.","DOI":"10.1002\/9783527692156.ch28"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8445","DOI":"10.1021\/bi700028u","article-title":"Bone morphogenetic protein-1 (BMP-1) cleaves human proapolipoprotein A1 and regulates its activation for lipid binding","volume":"46","author":"Chau","year":"2007","journal-title":"Biochemistry"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Davidson, W.S., Shah, A.S., Sexmith, H., and Gordon, S.M. (2022). The HDL Proteome Watch: Compilation of studies leads to new insights on HDL function. Biochim. Biophys. Acta BBA\u2014Mol. Cell Biol. Lipids, 1867.","DOI":"10.1016\/j.bbalip.2021.159072"},{"key":"ref_23","unstructured":"Davidson, W.S. (2024, August 30). HDL Proteome Watch. Available online: https:\/\/homepages.uc.edu\/~davidswm\/HDLproteome.html."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1530\/jrf.0.0820813","article-title":"Physiological factors underlying the formation of ovarian follicular fluid","volume":"82","author":"Gosden","year":"1988","journal-title":"Reproduction"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1095\/biolreprod.109.082941","article-title":"Formation of the ovarian follicular antrum and follicular fluid","volume":"82","author":"Rodgers","year":"2010","journal-title":"Biol. Reprod."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1530\/REP-07-0062","article-title":"Involvement of follicular basement membrane and vascular endothelium in blood\u2013follicle barrier formation of mice revealed by \u2018in vivo cryotechnique\u2019","volume":"134","author":"Zhou","year":"2007","journal-title":"Reproduction"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kontush, A., Lindahl, M., Lhomme, M., Calabresi, L., Chapman, M.J., and Davidson, W.S. (2015). Structure of HDL: Particle subclasses and molecular components. High Density Lipoproteins: From Biological Understanding to Clinical Exploitation, Springer.","DOI":"10.1007\/978-3-319-09665-0_1"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/S0022-2275(20)38108-6","article-title":"Distribution of high density lipoprotein particles with different apoprotein composition: Particles with AI and A-II and particles with AI but no A-II","volume":"23","author":"Cheung","year":"1982","journal-title":"J. Lipid Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1016\/j.bbapap.2006.09.001","article-title":"Proteome analysis of human follicular fluid","volume":"1764","author":"Angelucci","year":"2006","journal-title":"Biochim. Biophys. Acta BBA\u2014Proteins Proteom."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1194\/jlr.M041038","article-title":"Evidence for the presence of lipid-free monomolecular apolipoprotein A-1 in plasma","volume":"55","author":"Miyazaki","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1160\/TH13-02-0178","article-title":"Proteome of human plasma very low-density lipoprotein and low-density lipoprotein exhibits a link with coagulation and lipid metabolism","volume":"112","author":"Dashty","year":"2014","journal-title":"Thromb. Haemost."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1161\/CIRCOUTCOMES.113.000675","article-title":"High-density lipoprotein particle subclass heterogeneity and incident coronary heart disease","volume":"7","author":"Akinkuolie","year":"2014","journal-title":"Circ. Cardiovasc. Qual. Outcomes"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zhang, M., Charles, R., Tong, H., Zhang, L., Patel, M., Wang, F., Rames, M.J., Ren, A., Rye, K.A., and Qiu, X. (2015). HDL surface lipids mediate CETP binding as revealed by electron microscopy and molecular dynamics simulation. Sci. Rep., 5.","DOI":"10.1038\/srep08741"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.1016\/j.fertnstert.2008.12.129","article-title":"Age-related variations in follicular apolipoproteins may influence human oocyte maturation and fertility potential","volume":"93","author":"Monisova","year":"2010","journal-title":"Fertil. Steril."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1210\/jc.2007-1756","article-title":"A more atherogenic serum lipoprotein profile is present in women with polycystic ovary syndrome: A case-control study","volume":"93","author":"Valkenburg","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/j.1365-2265.1992.tb02295.x","article-title":"Risk factors for coronary artery disease in lean and obese women with the polycystic ovary syndrome","volume":"37","author":"Conway","year":"1992","journal-title":"Clin. Endocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"137","DOI":"10.5468\/ogs.2013.56.3.137","article-title":"Dyslipidemia in women with polycystic ovary syndrome","volume":"56","author":"Kim","year":"2013","journal-title":"Obstet. Gynecol. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e2928","DOI":"10.1210\/clinem\/dgab234","article-title":"HDL containing apolipoprotein C-III is associated with insulin sensitivity: A multicenter cohort study","volume":"106","author":"Yamamoto","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_39","first-page":"1409","article-title":"Proteomics analysis of potential serum biomarkers for insulin resistance in patients with polycystic ovary syndrome","volume":"45","author":"Li","year":"2020","journal-title":"Int. J. Mol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"707","DOI":"10.3892\/ijmm.2013.1250","article-title":"Apolipoprotein A-IV as a novel gene associated with polycystic ovary syndrome","volume":"31","author":"Kim","year":"2013","journal-title":"Int. J. Mol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1172\/JCI110253","article-title":"Alpha2-plasmin inhibitor and alpha2-macroglobulin-plasmin complexes in plasma. Quantitation by an enzyme-linked differential antibody immunosorbent assay","volume":"68","author":"Harpel","year":"1981","journal-title":"J. Clin. Investig."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/978-1-4615-5391-5_3","article-title":"Antithrombin: A bloody important serpin","volume":"425","author":"Olson","year":"1997","journal-title":"Chem. Biol. Serpins"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/0006-291X(69)90278-2","article-title":"Activation of plasminogen by human plasma kallikrein","volume":"35","author":"Colman","year":"1969","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/0955-2235(95)00012-7","article-title":"Insulin-like growth factor binding protein (IGFBP) proteases: Functional regulators of cell growth","volume":"6","author":"Rajah","year":"1995","journal-title":"Prog. Growth Factor Res."},{"key":"ref_45","first-page":"1","article-title":"Bioregulation of kinins: Kallikreins, kininogens, and kininases","volume":"44","author":"Bhoola","year":"1992","journal-title":"Pharmacol. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1080\/19490992.2015.1054092","article-title":"Myosin light chains: Teaching old dogs new tricks","volume":"4","author":"Heissler","year":"2014","journal-title":"Bioarchitecture"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.ejogrb.2013.01.013","article-title":"Use of ovarian reserve parameters for predicting live births in women undergoing in vitro fertilization","volume":"168","author":"Lukaszuk","year":"2013","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4359","DOI":"10.1021\/acs.jproteome.5b00543","article-title":"The use of variable Q1 isolation windows improves selectivity in LC\u2013SWATH\u2013MS acquisition","volume":"14","author":"Zhang","year":"2015","journal-title":"J. Proteome Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Przewocki, J., Kossi\u0144ski, D., ukaszuk, A., Jakiel, G., Woc\u0142awek-Potocka, I., O\u0142dziej, S., and ukaszuk, K. (2024). Follicular Fluid Proteomic Analysis to Identify Predictive Markers of Normal Embryonic Development. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25158431"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/21\/11749\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:26:29Z","timestamp":1760113589000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/21\/11749"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,1]]},"references-count":49,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["ijms252111749"],"URL":"https:\/\/doi.org\/10.3390\/ijms252111749","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,1]]}}}