{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:52:43Z","timestamp":1791420763059,"version":"4.3.3"},"reference-count":80,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"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>Matrix metalloproteinases (MMPs) are M2 macrophage markers that are modulated by inflammation. A disintegrin and metalloproteinases (ADAMS) and those with thrombospondin motifs (ADAMTS) regulate the shedding of membrane-bound proteins, growth factors, cytokines, ligands, and receptors; MMPs, ADAMS, and ADAMTS may be regulated by tissue inhibitors of metalloproteinases (TIMPs). This study aimed to determine whether these interacting proteins were dysregulated in PCOS. A Somascan proteomic analysis of 12 MMPs, three of their inhibitors (TIMP-1, 2, 3), two ADAMS (9, 12), five ADAMTS (1, 4, 5, 13, 15), insulin-like growth factor binding protein-1 (IGFBP-1), and insulin-like growth factor-1 (IGF-1) was undertaken in a well-validated PCOS database of 143 women with PCOS and 97 controls. Women with PCOS had significantly higher levels of MMP-9 and lower levels of MMP-2, MMP-14, TIMP-2, IGFBP-1, and IGF-1 compared to the controls (p &lt; 0.0001, p &lt; 0.005, p &lt; 0.04, p &lt; 0.05, p &lt; 0.0001, and p &lt; 0.0001, respectively). No differences were observed for any other MMPs. The ADAMS or ADAMTS levels did not differ between groups. Body mass index (BMI) was correlated with MMP-9 (p &lt; 0.01), MMP-1 (p &lt; 0.05), MMP-2 (p &lt; 0.05), MMP-10 (p &lt; 0.005), MMP-12 (p &lt; 0.005), ADAM-9 (p &lt; 0.05), and IGFBP-1 (p &lt; 0.0001), but only MMP-9 still differed after accounting for BMI. MMP-9\/TIMP-1, MMP-9\/TIMP-2, and MMP-9\/TIMP-3 ratios were higher in the PCOS group (p &lt; 0.01), whilst MMP-17\/TIMP-1 and MMP-17\/TIMP-2 were lower (p = 0.01). MMP-2\/TIMP ratios showed no difference between groups. TIMP-2 was positively correlated with CRP (p &lt; 0.01). MMP changes in PCOS are largely driven by BMI, though increased MMP-9 is BMI-independent, suggesting that any deleterious effects of MMP-9 would be potentially exacerbated by a concomitantly increased BMI. The significant increases in the MMP-9\/TIMP ratios suggests MMP-9 overactivity in PCOS.<\/jats:p>","DOI":"10.3390\/ijms26010321","type":"journal-article","created":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T11:24:19Z","timestamp":1735730659000},"page":"321","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Matrix Metalloproteinases, Tissue Inhibitors of Metalloproteinases, and Their Ratios in Women with Polycystic Ovary Syndrome and Healthy Controls"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5762-3917","authenticated-orcid":false,"given":"Alexandra E.","family":"Butler","sequence":"first","affiliation":[{"name":"Research Department, Royal College of Surgeons of Ireland, Adliya 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjula","family":"Nandakumar","sequence":"additional","affiliation":[{"name":"Research Department, Royal College of Surgeons of Ireland, Adliya 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":"Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Hull HU6 7RX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0183-4683","authenticated-orcid":false,"given":"Edwina","family":"Brennan","sequence":"additional","affiliation":[{"name":"Research Department, Royal College of Surgeons of Ireland, Adliya 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 of Ireland, Adliya 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/nrc.2016.115","article-title":"TIMPs: Versatile extracellular regulators in cancer","volume":"17","author":"Jackson","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.pmbts.2017.02.005","article-title":"Biochemical and Biological Attributes of Matrix Metalloproteinases","volume":"147","author":"Cui","year":"2017","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"148990","DOI":"10.1016\/j.gene.2024.148990","article-title":"Matrix metalloproteinases: Master regulators of tissue morphogenesis","volume":"933","author":"Sreesada","year":"2025","journal-title":"Gene"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1172\/JCI6870","article-title":"Matrix metalloproteinases in angiogenesis: A moving target for therapeutic intervention","volume":"103","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"28","DOI":"10.4103\/0973-1482.157337","article-title":"Seesaw of matrix metalloproteinases (MMPs)","volume":"12","author":"Kapoor","year":"2016","journal-title":"J. Cancer Res. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1002\/dvdy.398","article-title":"Emerging roles of MT-MMPs in embryonic development","volume":"251","author":"Moracho","year":"2022","journal-title":"Dev. Dyn."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nrm2125","article-title":"Matrix metalloproteinases and the regulation of tissue remodelling","volume":"8","author":"Ewald","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.matbio.2015.01.012","article-title":"Multilevel regulation of matrix metalloproteinases in tissue homeostasis indicates their molecular specificity in vivo","volume":"44\u201346","author":"Gaffney","year":"2015","journal-title":"Matrix Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/112_2021_67","article-title":"The Biochemistry and Physiology of A Disintegrin and Metalloproteinases (ADAMs and ADAM-TSs) in Human Pathologies","volume":"184","author":"Sharma","year":"2023","journal-title":"Rev. Physiol. Biochem. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.matbio.2015.03.005","article-title":"The role of TIMPs in regulation of extracellular matrix proteolysis","volume":"44\u201346","author":"Arpino","year":"2015","journal-title":"Matrix Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/nri3499","article-title":"Metalloproteinases and their natural inhibitors in inflammation and immunity","volume":"13","author":"Khokha","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Serra, R. (2020). Matrix Metalloproteinases in Health and Disease. Biomolecules, 10.","DOI":"10.3390\/biom10081138"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Moli\u00e8re, S., Jaulin, A., Tomasetto, C.L., and Dali-Youcef, N. (2023). Roles of Matrix Metalloproteinases and Their Natural Inhibitors in Metabolism: Insights into Health and Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241310649"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Costa, D., Scalise, E., Ielapi, N., Bracale, U.M., Andreucci, M., and Serra, R. (2024). Metalloproteinases as Biomarkers and Sociomarkers in Human Health and Disease. Biomolecules, 14.","DOI":"10.3390\/biom14010096"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Cabral-Pacheco, G.A., Garza-Veloz, I., Castruita-De la Rosa, C., Ramirez-Acu\u00f1a, J.M., Perez-Romero, B.A., Guerrero-Rodriguez, J.F., Martinez-Avila, N., and Martinez-Fierro, M.L. (2020). The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249739"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/bs.apha.2017.08.002","article-title":"Matrix Metalloproteinases, Vascular Remodeling, and Vascular Disease","volume":"81","author":"Wang","year":"2018","journal-title":"Adv. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1002\/cphy.c140045","article-title":"Extracellular matrix communication and turnover in cardiac physiology and pathology","volume":"5","author":"Takawale","year":"2015","journal-title":"Compr. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1186\/s40001-023-01094-7","article-title":"The usefulness of MMP-9, TIMP-1 and MMP-9\/TIMP-1 ratio for diagnosis and assessment of COPD severity","volume":"28","author":"Hoda","year":"2023","journal-title":"Eur. J. Med. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1055\/s-2007-992925","article-title":"Implications of polycystic ovary syndrome on oocyte development","volume":"26","author":"Dumesic","year":"2008","journal-title":"Semin. Reprod. Med."},{"key":"ref_20","first-page":"173","article-title":"Vitrification affects the expression of matrix metalloproteinases and their tissue inhibitors of mouse ovarian tissue","volume":"14","author":"Asadzadeh","year":"2016","journal-title":"Int. J. Reprod. Biomed."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.2741\/1409","article-title":"MMPS and TIMPS in ovarian physiology and pathophysiology","volume":"9","author":"Goldman","year":"2004","journal-title":"Front. Biosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1530\/REP-15-0340","article-title":"Matrix metalloproteinases 2 and 9 and MMP9\/NGAL complex activity in women with PCOS","volume":"151","author":"Ranjbaran","year":"2016","journal-title":"Reproduction"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1080\/09513590802056995","article-title":"Raised serum levels of matrix metalloproteinase-9 in women with polycystic ovary syndrome and its association with insulin-like growth factor binding protein-1","volume":"24","author":"Liu","year":"2008","journal-title":"Gynecol. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.ijgo.2006.11.012","article-title":"Elevated serum levels of matrix metalloproteinase-2 in women with polycystic ovarian syndrome","volume":"96","author":"Liu","year":"2007","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1093\/humrep\/dew218","article-title":"The prevalence and phenotypic features of polycystic ovary syndrome: A systematic review and meta-analysis","volume":"31","author":"Bozdag","year":"2016","journal-title":"Hum. Reprod."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"39.e1","DOI":"10.1016\/j.ajog.2023.04.010","article-title":"Incidence, prevalence, and trends in polycystic ovary syndrome diagnosis: A United States population-based study from 2006 to 2019","volume":"229","author":"Yu","year":"2023","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s11010-011-0793-6","article-title":"Imbalanced circulating matrix metalloproteinases in polycystic ovary syndrome","volume":"353","author":"Gomes","year":"2011","journal-title":"Mol. Cell. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1210\/jc.2005-0648","article-title":"Increased circulating levels of matrix metalloproteinase-2 and -9 in women with the polycystic ovary syndrome","volume":"91","author":"Lewandowski","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/S0015-0282(02)04838-0","article-title":"Decreased expression of tissue inhibitor of matrix metalloproteinases in follicular fluid from women with polycystic ovaries compared with normally ovulating patients undergoing in vitro fertilization","volume":"79","author":"Kraiem","year":"2003","journal-title":"Fertil. Steril."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1530\/EJE-07-0822","article-title":"Serum concentrations of atherogenic proteins neutrophil gelatinase-associated lipocalin and its complex with matrix metalloproteinase-9 are significantly lower in women with polycystic ovary syndrome: Hint of a protective mechanism?","volume":"158","author":"Livadas","year":"2008","journal-title":"Eur. J. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Moin, A.S.M., Sathyapalan, T., Butler, A.E., and Atkin, S.L. (2021). Vitamin D Association With Macrophage-Derived Cytokines in Polycystic Ovary Syndrome: An Enhanced Risk of COVID-19 Infection?. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.638621"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.bcp.2019.03.033","article-title":"A Disintegrin and Metalloproteinase (ADAM) and ADAM with thrombospondin motifs (ADAMTS) family in vascular biology and disease","volume":"164","author":"Zhong","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Yang, G., Yao, G., Xu, Z., Fan, H., Liu, X., He, J., Kong, Y., Kong, D., Bai, Y., and He, Q. (2021). Expression Level of ADAMTS1 in Granulosa Cells of PCOS Patients Is Related to Granulosa Cell Function, Oocyte Quality, and Embryo Development. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.647522"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"E1015","DOI":"10.1210\/jc.2013-4177","article-title":"Evidence for decreased expression of ADAMTS-1 associated with impaired oocyte quality in PCOS patients","volume":"99","author":"Xiao","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"24","DOI":"10.4274\/jcrpe.3414","article-title":"Role of Versican and ADAMTS-1 in Polycystic Ovary Syndrome","volume":"9","author":"Tokmak","year":"2017","journal-title":"J. Clin. Res. Pediatr. Endocrinol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Shi, Y., Shi, Y., He, G., Wang, G., Liu, H., and Shao, X. (2022). Association of ADAMTS proteoglycanases downregulation with IVF-ET outcomes in patients with polycystic ovary syndrome: A systematic review and meta-analysis. Reprod. Biol. Endocrinol., 20.","DOI":"10.1186\/s12958-022-01035-9"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"575","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":"ref_38","doi-asserted-by":"crossref","unstructured":"Armanini, D., Boscaro, M., Bordin, L., and Sabbadin, C. (2022). Controversies in the Pathogenesis, Diagnosis and Treatment of PCOS: Focus on Insulin Resistance, Inflammation, and Hyperandrogenism. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23084110"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.bbrc.2005.06.010","article-title":"Matrix metalloproteinase-7 degrades all insulin-like growth factor binding proteins and facilitates insulin-like growth factor bioavailability","volume":"333","author":"Nakamura","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1515\/med-2020-0216","article-title":"IGF-1 regulates the growth of fibroblasts and extracellular matrix deposition in pelvic organ prolapse","volume":"15","author":"Yin","year":"2020","journal-title":"Open Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.jpag.2014.07.016","article-title":"The Polycystic Ovary Morphology-Polycystic Ovary Syndrome Spectrum","volume":"28","author":"Rosenfield","year":"2015","journal-title":"J. Pediatr. Adolesc. Gynecol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1177\/1933719107309818","article-title":"The role of the extracellular matrix in ovarian follicle development","volume":"14","author":"Woodruff","year":"2007","journal-title":"Reprod. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1210\/er.2006-0022","article-title":"The Molecular Control of Corpus Luteum Formation, Function, and Regression","volume":"28","author":"Stocco","year":"2007","journal-title":"Endocr. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.matbio.2015.01.005","article-title":"Matrix metalloproteinase interactions with collagen and elastin","volume":"44-46","year":"2015","journal-title":"Matrix Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/j.1440-1827.2010.02547.x","article-title":"Matrix metalloproteinases, a disintegrin and metalloproteinases, and a disintegrin and metalloproteinases with thrombospondin motifs in non-neoplastic diseases","volume":"60","author":"Shiomi","year":"2010","journal-title":"Pathol. Int."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s10875-006-9022-6","article-title":"Matrix Metalloproteinase-9 and Autoimmune Diseases","volume":"26","author":"Ram","year":"2006","journal-title":"J. Clin. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Caban, M., Owczarek, K., and Lewandowska, U. (2022). The Role of Metalloproteinases and Their Tissue Inhibitors on Ocular Diseases: Focusing on Potential Mechanisms. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23084256"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1093\/molehr\/7.4.325","article-title":"The balance between MMP-9 and MMP-2 and their tissue inhibitor (TIMP)-1 in luteinized granulosa cells: Comparison between women with PCOS and normal ovulatory women","volume":"7","author":"Shalev","year":"2001","journal-title":"Mol. Hum. Reprod."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/S0015-0282(02)04814-8","article-title":"Regulation of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of MMP, and progesterone secretion in luteinized granulosa cells from normally ovulating women with polycystic ovary disease","volume":"79","author":"Goldman","year":"2003","journal-title":"Fertil. Steril."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/molehr\/gah003","article-title":"Differences in connective tissue gene expression between normally functioning, polycystic and post-menopausal ovaries","volume":"10","author":"Oksjoki","year":"2004","journal-title":"Mol. Hum. Reprod."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1530\/REP-22-0295","article-title":"OONO-\/MMP2\/MMP9 pathway-mediated apoptosis of porcine granulosa cells is associated with DNA damage","volume":"165","author":"Lei","year":"2023","journal-title":"Reproduction"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Moin, A.S., Sathyapalan, T., Atkin, S.L., and Butler, A.E. (2022). Inflammatory Markers in Non-Obese Women with Polycystic Ovary Syndrome Are Not Elevated and Show No Correlation with Vitamin D Metabolites. Nutrients, 14.","DOI":"10.3390\/nu14173540"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Akram, Z., Mahjabeen, I., Irshad, F., Ahmed, M.W., Rehman, S., Rizwan, M., Shafqat, A., Kiran, A., and Saeed, A. (2022). Expression deregulation of matrix metalloproteinases and vasoconstriction related genes in Pakistani females with abnormal uterine bleeding. BMC Womens Health, 22.","DOI":"10.1186\/s12905-022-02132-y"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1021\/ja003579+","article-title":"Identification of a novel class of small-molecule antiangiogenic agents through the screening of combinatorial libraries which function by inhibiting the binding and localization of proteinase MMP2 to integrin alpha(V)beta(3)","volume":"123","author":"Boger","year":"2001","journal-title":"J. Am. Chem. Soc."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.cytogfr.2017.01.003","article-title":"Crosstalk between insulin-like growth factor (IGF) receptor and integrins through direct integrin binding to IGF1","volume":"34","author":"Takada","year":"2017","journal-title":"Cytokine Growth Factor. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.lab.2005.07.010","article-title":"C-reactive protein increases matrix metalloproteinase-2 expression and activity in cultured human vascular smooth muscle cells","volume":"146","author":"Doronzo","year":"2005","journal-title":"J. Lab. Clin. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.lfs.2018.11.036","article-title":"Genistein inhibits Ang II-induced CRP and MMP-9 generations via the ER-p38\/ERK1\/2-PPAR\u03b3-NF-\u03baB signaling pathway in rat vascular smooth muscle cells","volume":"216","author":"Xu","year":"2019","journal-title":"Life Sci."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Aboeldalyl, S., James, C., Seyam, E., Ibrahim, E.M., Shawki, H.E., and Amer, S. (2021). The Role of Chronic Inflammation in Polycystic Ovarian Syndrome-A Systematic Review and Meta-Analysis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052734"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Boumiza, S., Chahed, K., Tabka, Z., Jacob, M.P., Norel, X., and Ozen, G. (2021). MMPs and TIMPs levels are correlated with anthropometric parameters, blood pressure, and endothelial function in obesity. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-99577-2"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.matbio.2023.10.002","article-title":"Mmp14 is required for matrisome homeostasis and circadian rhythm in fibroblasts","volume":"124","author":"Yeung","year":"2023","journal-title":"Matrix Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"154892","DOI":"10.1016\/j.prp.2023.154892","article-title":"Assessment of MMP14, CAV2, CLU and SPARCL1 expression profiles in endometriosis","volume":"251","author":"Pant","year":"2023","journal-title":"Pathol. Res. Pract."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Yip, C., Foidart, P., No\u00ebl, A., and Sounni, N.E. (2019). MT4-MMP: The GPI-Anchored Membrane-Type Matrix Metalloprotease with Multiple Functions in Diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020354"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s10555-008-9129-8","article-title":"MT4-(MMP17) and MT6-MMP (MMP25), A unique set of membrane-anchored matrix metalloproteinases: Properties and expression in cancer","volume":"27","author":"Sohail","year":"2008","journal-title":"Cancer Metastasis Rev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/molehr\/gah257","article-title":"Membrane-type matrix metalloproteinases and vascularization in human endometrium during the menstrual cycle","volume":"12","author":"Plaisier","year":"2006","journal-title":"Mol. Human Reprod."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"R199","DOI":"10.1530\/REP-17-0597","article-title":"Ovarian angiogenesis in polycystic ovary syndrome","volume":"155","author":"Pascuali","year":"2018","journal-title":"Reproduction"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.eprac.2022.12.004","article-title":"Association of Insulin-Like Growth Factor-1 With Polycystic Ovarian Syndrome: A Systematic Review and Meta-analysis","volume":"29","author":"Li","year":"2023","journal-title":"Endocr. Pract."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"350","DOI":"10.3390\/endocrines4020027","article-title":"The Androgen Regulation of Matrix Metalloproteases in Prostate Cancer and Its Related Tumor Microenvironment","volume":"4","author":"Sorrentino","year":"2023","journal-title":"Endocrines"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"299","DOI":"10.5694\/mja18.00635","article-title":"A new evidence-based guideline for assessment and management of polycystic ovary syndrome","volume":"209","author":"Norman","year":"2018","journal-title":"Med. J. Aust."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Kim, C.H., and Lee, S.H. (2022). Effectiveness of Lifestyle Modification in Polycystic Ovary Syndrome Patients with Obesity: A Systematic Review and Meta-Analysis. Life, 12.","DOI":"10.3390\/life12020308"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Ee, C., Pirotta, S., Mousa, A., Moran, L., and Lim, S. (2021). Providing lifestyle advice to women with PCOS: An overview of practical issues affecting success. BMC Endocr. Disord., 21.","DOI":"10.1186\/s12902-021-00890-8"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1007\/s11695-013-1111-z","article-title":"Serum SPARC and matrix metalloproteinase-2 and metalloproteinase-9 concentrations after bariatric surgery in obese adults","volume":"24","author":"Lee","year":"2014","journal-title":"Obes. Surg."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"493.e1","DOI":"10.1016\/j.ajog.2017.01.003","article-title":"Racial and ethnic differences in the polycystic ovary syndrome metabolic phenotype","volume":"216","author":"Engmann","year":"2017","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"77","DOI":"10.59653\/jhsmt.v2i02.632","article-title":"The Role of ADAM17 in PCOS Pathogenesis: A review Paper","volume":"2","author":"Preap","year":"2024","journal-title":"J. Health Sci. Med. Ther."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s00404-018-4967-2","article-title":"Abnormal expressions of ADAMTS-1, ADAMTS-9 and progesterone receptors are associated with lower oocyte maturation in women with polycystic ovary syndrome","volume":"299","author":"GohariTaban","year":"2019","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/cen.13517","article-title":"Anti-Mullerian hormone measurement for the diagnosis of polycystic ovary syndrome","volume":"88","author":"Sathyapalan","year":"2018","journal-title":"Clin. Endocrinol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"The Rotterdam ESHRE\/ASRM-Sponsored PCOS Consensus Workshop Group (2004). Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil. Steril., 81, 19\u201325.","DOI":"10.1016\/j.fertnstert.2003.10.004"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Kahal, H., Halama, A., Aburima, A., Bhagwat, A.M., Butler, A.E., Grauman, J., Suhre, K., Sathyapalan, T., and Atkin, S.L. (2020). Effect of induced hypoglycemia on inflammation and oxidative stress in type 2 diabetes and control subjects. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-61531-z"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Gold, L., Ayers, D., Bertino, J., Bock, C., Bock, A., Brody, E.N., Carter, J., Dalby, A.B., Eaton, B.E., and Fitzwater, T. (2010). Aptamer-based multiplexed proteomic technology for biomarker discovery. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0015004"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"14357","DOI":"10.1038\/ncomms14357","article-title":"Connecting genetic risk to disease end points through the human blood plasma proteome","volume":"8","author":"Suhre","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Kraemer, S., Vaught, J.D., Bock, C., Gold, L., Katilius, E., Keeney, T.R., Kim, N., Saccomano, N.A., Wilcox, S.K., and Zichi, D. (2011). From SOMAmer-based biomarker discovery to diagnostic and clinical applications: A SOMAmer-based, streamlined multiplex proteomic assay. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026332"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/1\/321\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T15:23:18Z","timestamp":1759850598000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/1\/321"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,1]]},"references-count":80,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["ijms26010321"],"URL":"https:\/\/doi.org\/10.3390\/ijms26010321","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,1]]}}}