{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:47:34Z","timestamp":1753890454835,"version":"3.41.2"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T00:00:00Z","timestamp":1699401600000},"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. Cell Dev. Biol."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> The aim of this study was to analyze and compare the differential expression of peptides within the follicular fluid of polycystic ovary syndrome (PCOS) patients <jats:italic>versus<\/jats:italic> normal women by using peptidomics techniques. The underlying mechanisms involved in PCOS pathogenesis will be explored, together with screening and identification of potential functional peptides via bioinformatics analysis.<\/jats:p><jats:p><jats:bold>Materials and methods:<\/jats:bold> A total of 12 patients who underwent <jats:italic>in vitro<\/jats:italic> fertilization and embryo transfer (IVF-ET) at the Reproductive Medicine Center of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from 1 September 2022 to 1 November 2022 were included in this study. The follicular fluid of PCOS patients (<jats:italic>n<\/jats:italic> = 6) and normal women (<jats:italic>n<\/jats:italic> = 6) were collected. The presence and concentration differences of various peptides were detected by the LC-MS\/MS method. GO and KEGG analysis were performed on the precursor proteins of the differentially-expressed peptides, and protein network interaction analysis was carried out to identify functionally-relevant peptides among the various peptides.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> A variety of peptides within the follicular fluid of PCOS <jats:italic>versus<\/jats:italic> normal patients were detected by peptidomics techniques. Altogether, 843 upregulated peptides and 236 downregulated peptides were detected (absolute fold change \u22652 and <jats:italic>p<\/jats:italic> &amp;lt; 0.05). Of these, 718 (718 = 488 + 230) peptides were only detected in the PCOS group, while 205 (205 = 174 + 31) were only detected in the control group. Gene Ontology enrichment and pathway analysis were performed to characterize peptides through their precursor proteins. We identified 18 peptides from 7 precursor proteins associated with PCOS, and 4 peptide sequences were located in the functional domains of their corresponding precursor proteins.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> In this study, differences in the follicular development of PCOS <jats:italic>versus<\/jats:italic> normal patients were revealed from the polypeptidomics of follicular development, which thus provided new insights for future studies on the pathological mechanisms of PCOS development.<\/jats:p>","DOI":"10.3389\/fcell.2023.1289063","type":"journal-article","created":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T05:40:21Z","timestamp":1700026821000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Peptidomic analysis of follicular fluid in patients with polycystic ovarian syndrome"],"prefix":"10.3389","volume":"11","author":[{"given":"Ningyu","family":"Sun","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wuwen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lihua","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boon Chin","family":"Heng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiwei","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yin","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoqing","family":"Tong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1080\/09513590.2018.1512967","article-title":"Asprosin: a novel peptide hormone related to insulin resistance in women with polycystic ovary syndrome","volume":"35","author":"Alan","year":"2019","journal-title":"Gynecol. Endocrinol. Off. J. Int. Soc. Gynecol. Endocrinol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1002\/1522-2683(200204)23:7\/8<1197::AID-ELPS1197>3.0.CO;2-2","article-title":"Identification of new proteins in follicular fluid of mature human follicles","volume":"23","author":"Anahory","year":"2002","journal-title":"Electrophoresis"},{"key":"B3","doi-asserted-by":"publisher","first-page":"7105","DOI":"10.1021\/bi00243a010","article-title":"An in vitro novel mechanism of regulating the activity of pyruvate kinase M2 by thyroid hormone and fructose 1, 6-bisphosphate","volume":"30","author":"Ashizawa","year":"1991","journal-title":"Biochemistry"},{"key":"B4","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1080\/09513590.2019.1665646","article-title":"Decreased levels of liver-expressed antimicrobial peptide-2 and ghrelin are related to insulin resistance in women with polycystic ovary syndrome","volume":"36","author":"Aslanipour","year":"2020","journal-title":"Gynecol. Endocrinol. Off. J. Int. Soc. Gynecol. Endocrinol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"104","DOI":"10.2741\/e695","article-title":"Polycystic ovary syndrome: current status and future perspective","volume":"6","author":"Barthelmess","year":"2014","journal-title":"Front. Biosci. Elite"},{"key":"B6","doi-asserted-by":"publisher","first-page":"38","DOI":"10.5935\/1518-0557.20160009","article-title":"Human follicular fluid and effects on reproduction","volume":"20","author":"Basuino","year":"2016","journal-title":"JBRA Assist. Reprod."},{"key":"B7","doi-asserted-by":"publisher","first-page":"935","DOI":"10.2337\/diabetes.52.4.935","article-title":"Defective signaling through Akt-2 and -3 but not Akt-1 in insulin-resistant human skeletal muscle: potential role in insulin resistance","volume":"52","author":"Brozinick","year":"2003","journal-title":"Diabetes"},{"key":"B8","doi-asserted-by":"publisher","first-page":"16306","DOI":"10.1038\/s41598-019-52856-5","article-title":"Expression of microRNA in follicular fluid in women with and without PCOS","volume":"9","author":"Butler","year":"2019","journal-title":"Sci. Rep."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1016\/j.jmb.2007.07.018","article-title":"Reconstitution of the mitochondrial PrxIII antioxidant defence pathway: general properties and factors affecting PrxIII activity and oligomeric state","volume":"372","author":"Cao","year":"2007","journal-title":"J. Mol. Biol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e2695","DOI":"10.1210\/clinem\/dgaa285","article-title":"Obesity, polycystic ovary syndrome, and infertility: a new avenue for GLP-1 receptor agonists","volume":"105","author":"Cena","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B11","first-page":"117","article-title":"Ovarian follicular and luteal physiology","volume":"22","author":"Channing","year":"1980","journal-title":"Int. Rev. Physiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1080\/09513590.2021.1958310","article-title":"Polycystic ovarian syndrome and infertility: overview and insights of the putative treatments","volume":"37","author":"Coll\u00e9e","year":"2021","journal-title":"Gynecol. Endocrinol. Off. J. Int. Soc. Gynecol. Endocrinol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"3674","DOI":"10.1093\/bioinformatics\/bti610","article-title":"Blast2GO: a universal tool for annotation, visualization and analysis in functional genomics research","volume":"21","author":"Conesa","year":"2005","journal-title":"Bioinforma. Oxf Engl."},{"key":"B14","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1007\/s10815-018-1143-3","article-title":"Influence of follicular fluid and cumulus cells on oocyte quality: clinical implications","volume":"35","author":"Da Broi","year":"2018","journal-title":"R"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2079","DOI":"10.1021\/pr060225u","article-title":"Peptidomics for cancer diagnosis: present and future","volume":"5","author":"Diamandis","year":"2006","journal-title":"J. Proteome Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"9417","DOI":"10.1021\/bi0474923","article-title":"Structural basis for tumor pyruvate kinase M2 allosteric regulation and catalysis","volume":"44","author":"Dombrauckas","year":"2005","journal-title":"Biochemistry"},{"key":"B17","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1517\/13543771003627464","article-title":"Non-erythropoietic tissue-protective peptides derived from erythropoietin: WO2009094172","volume":"20","author":"Dumont","year":"2010","journal-title":"Expert Opin. Ther. Pat."},{"key":"B18","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1016\/j.yjmcc.2010.08.011","article-title":"Akt2 deficiency promotes cardiac induction of Rab4a and myocardial \u03b2-adrenergic hypersensitivity","volume":"49","author":"Etzion","year":"2010","journal-title":"J. Mol. Cell Cardiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"5637","DOI":"10.1038\/srep05637","article-title":"PEDF and PEDF-derived peptide 44mer protect cardiomyocytes against hypoxia-induced apoptosis and necroptosis via anti-oxidative effect","volume":"4","author":"Gao","year":"2014","journal-title":"Sci. Rep."},{"key":"B20","doi-asserted-by":"publisher","first-page":"449","DOI":"10.18502\/ijrm.v19i5.9254","article-title":"Follicular fluid oxidative stress biomarkers and ART outcomes in PCOS women undergoing in vitro fertilization: a cross-sectional study","volume":"19","author":"Gongadashetti","year":"2021","journal-title":"Int. J. Reprod. Biomed."},{"key":"B21","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/nrm.2016.25","article-title":"Metabolomics: beyond biomarkers and towards mechanisms","volume":"17","author":"Johnson","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"5885","DOI":"10.1002\/jcp.26393","article-title":"Analysis of secreted peptidome from omental adipose tissue in polycystic ovarian syndrome patients","volume":"233","author":"Jia","year":"2018","journal-title":"J. Cell Physiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"463","DOI":"10.2147\/DMSO.S235011","article-title":"Identification of key genes involved in diabetic peripheral neuropathy progression and associated with pancreatic cancer","volume":"13","author":"Jian","year":"2020","journal-title":"Diabetes Metab. Syndr. Obes. Targets Ther."},{"key":"B24","doi-asserted-by":"publisher","first-page":"302","DOI":"10.2174\/156652410791065255","article-title":"Structure-function relationships of PEDF","volume":"10","author":"Kawaguchi","year":"2010","journal-title":"Curr. Mol. Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"10872","DOI":"10.1038\/s41598-018-28948-z","article-title":"GOATOOLS: a Python library for Gene Ontology analyses","volume":"8","author":"Klopfenstein","year":"2018","journal-title":"Sci. Rep."},{"key":"B26","doi-asserted-by":"publisher","first-page":"456","DOI":"10.3346\/jkms.2005.20.3.456","article-title":"Identification of new proteins in follicular fluid from mature human follicles by direct sample rehydration method of two-dimensional polyacrylamide gel electrophoresis","volume":"20","author":"Lee","year":"2005","journal-title":"J. Korean Med. Sci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"3053","DOI":"10.1021\/acs.jproteome.7b00366","article-title":"Qualitative and quantitative analysis of proteome and peptidome of human follicular fluid using multiple samples from single donor with LC-MS and SWATH methodology","volume":"16","author":"Lewandowska","year":"2017","journal-title":"J. Proteome Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2562","DOI":"10.1093\/humrep\/det262","article-title":"Prevalence of polycystic ovary syndrome in women in China: a large community-based study","volume":"28","author":"Li","year":"2013","journal-title":"Hum. Reprod. Oxf Engl."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1016\/j.fertnstert.2012.07.1131","article-title":"Metabolic profiling of follicular fluid and plasma from natural cycle in vitro fertilization patients--a pilot study","volume":"98","author":"McRae","year":"2012","journal-title":"Fertil. Steril."},{"key":"B30","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1007\/s00404-015-3976-7","article-title":"A systematic review of GLP-1 agonists on the metabolic syndrome in women with polycystic ovaries","volume":"293","author":"Niafar","year":"2016","journal-title":"Arch. Gynecol. Obstet."},{"key":"B31","doi-asserted-by":"publisher","first-page":"E2269","DOI":"10.1210\/jc.2013-3942","article-title":"Associations between insulin resistance, free fatty acids, and oocyte quality in polycystic ovary syndrome during in vitro fertilization","volume":"99","author":"Niu","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B32","doi-asserted-by":"publisher","first-page":"2133","DOI":"10.1152\/physrev.00063.2017","article-title":"Mechanisms of insulin action and insulin resistance","volume":"98","author":"Petersen","year":"2018","journal-title":"Physiol. Rev."},{"key":"B33","doi-asserted-by":"publisher","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":"B34","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1093\/brain\/awab071","article-title":"Biallelic loss-of-function variations in PRDX3 cause cerebellar ataxia","volume":"144","author":"Rebelo","year":"2021","journal-title":"Brain J. Neurol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1837","DOI":"10.3390\/nu13061837","article-title":"Foxtail millet improves blood glucose metabolism in diabetic rats through PI3K\/AKT and NF-\u03baB signaling pathways mediated by gut microbiota","volume":"13","author":"Ren","year":"2021","journal-title":"Nutrients"},{"key":"B36","doi-asserted-by":"publisher","first-page":"40","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. RBE"},{"key":"B37","doi-asserted-by":"publisher","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":"B38","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.fertnstert.2003.10.004","article-title":"Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome","volume":"81","year":"2004","journal-title":"Fertil. Steril."},{"key":"B39","doi-asserted-by":"publisher","first-page":"3068","DOI":"10.1210\/jc.2013-1715","article-title":"Identification of microRNAs in human follicular fluid: characterization of microRNAs that govern steroidogenesis in vitro and are associated with polycystic ovary syndrome in vivo","volume":"98","author":"Sang","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B40","doi-asserted-by":"publisher","first-page":"S55","DOI":"10.1016\/S0167-7799(01)01800-5","article-title":"Peptidomics technologies for human body fluids","volume":"19","author":"Schrader","year":"2001","journal-title":"Trends Biotechnol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"109453","DOI":"10.1016\/j.abb.2022.109453","article-title":"The follicular fluid metabolome in infertile individuals between polycystic ovary syndrome and diminished ovarian reserve","volume":"732","author":"Shen","year":"2022","journal-title":"Arch. Biochem. Biophys."},{"key":"B42","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1126\/science.278.5338.631","article-title":"A genomic perspective on protein families","volume":"278","author":"Tatusov","year":"1997","journal-title":"Science"},{"key":"B43","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1007\/s00404-017-4493-7","article-title":"Elevated circulating levels of xenopsin-related peptide-1 are associated with polycystic ovary syndrome","volume":"296","author":"Temur","year":"2017","journal-title":"Arch. Gynecol. Obstet."},{"key":"B44","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1042\/bj3070377","article-title":"Mammalian antioxidant protein complements alkylhydroperoxide reductase (ahpC) mutation in Escherichia coli","volume":"307","author":"Tsuji","year":"1995","journal-title":"Biochem. J."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1007\/s10815-013-0111-1","article-title":"An interleukin-6 gene promoter polymorphism is associated with polycystic ovary syndrome in South Indian women","volume":"30","author":"Tumu","year":"2013","journal-title":"J. Assist. Reprod. Genet."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1002\/pmic.201100240","article-title":"Proteomic analysis of the microenvironment of developing oocytes","volume":"12","author":"Twigt","year":"2012","journal-title":"Proteomics"},{"key":"B47","doi-asserted-by":"publisher","first-page":"4579831","DOI":"10.1155\/2022\/4579831","article-title":"Role of oxidative stress in obese and nonobese PCOS patients","volume":"2022","author":"U\u00e7kan","year":"2022","journal-title":"Int. J. Clin. Pract."},{"key":"B48","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/j.mito.2010.09.012","article-title":"Mitochondrial function in the human oocyte and embryo and their role in developmental competence","volume":"11","author":"Van Blerkom","year":"2011","journal-title":"Mitochondrion"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.1126\/science.1188015","article-title":"Evidence for an alternative glycolytic pathway in rapidly proliferating cells","volume":"329","author":"Vander Heiden","year":"2010","journal-title":"Science"},{"key":"B50","doi-asserted-by":"publisher","first-page":"956406","DOI":"10.3389\/fmolb.2022.956406","article-title":"Proteomics and bioinformatics analysis of follicular fluid from patients with polycystic ovary syndrome","volume":"9","author":"Wang","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"B51","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1159\/000456282","article-title":"Peptidomic analysis of cultured cardiomyocytes exposed to acute ischemic-hypoxia","volume":"41","author":"Wu","year":"2017","journal-title":"Cell Physiol. Biochem. Int. J. Exp. Cell Physiol. Biochem. Pharmacol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"W316","DOI":"10.1093\/nar\/gkr483","article-title":"KOBAS 2.0: a web server for annotation and identification of enriched pathways and diseases","volume":"39","author":"Xie","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"B53","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/j.bbrc.2018.02.093","article-title":"Quaternary structure influences the peroxidase activity of peroxiredoxin 3","volume":"497","author":"Yewdall","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B54","doi-asserted-by":"publisher","first-page":"e48613","DOI":"10.1371\/journal.pone.0048613","article-title":"Treatment with the proteasome inhibitor MG132 during the end of oocyte maturation improves oocyte competence for development after fertilization in cattle","volume":"7","author":"You","year":"2012","journal-title":"PloS One"}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2023.1289063\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T05:40:25Z","timestamp":1700026825000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2023.1289063\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,8]]},"references-count":54,"alternative-id":["10.3389\/fcell.2023.1289063"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2023.1289063","relation":{},"ISSN":["2296-634X"],"issn-type":[{"type":"electronic","value":"2296-634X"}],"subject":[],"published":{"date-parts":[[2023,11,8]]},"article-number":"1289063"}}