{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T01:58:42Z","timestamp":1792979922820,"version":"4.5.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Many components in follicular fluid (FF), such as peptide hormones, cytokines, and steroids, undergo dynamic changes during folliculogenesis and have important roles in follicular development. Because systemic inflammation has also been found to contribute to diminished ovarian reserve (DOR) in previous studies, do certain serum\/FF inflammatory biomarkers affect both follicular development and ovarian function?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Serum samples from the menstruation phase (n=26), serum samples from the ovulation phase (n=26), FF samples of mature oocytes (n=26), and FF samples of immature oocytes (n=10) were collected. Olink proteomic proximity extension assay (PEA) technology was used to compare the differentially expressed proteins (DEPs), and patients were divided into two subgroups\u2014the normal ovarian reserve (NOR) group and the DOR group\u2014for further bioinformatics analysis and verification by enzyme-linked immunosorbent assay (ELISA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In total, 16 DEPs were detected between the mature group and the immature group (FF), and 11 DEPs were detected between the ovulation group and the menstruation group (serum). Further subdivision of the ovarian reserve subgroups revealed 22 DEPs in FF and 3 DEPs in serum. Among all four comparisons, only the expression of oncostatin M (OSM) significantly differed. The OSM signaling pathway, the IL-10 anti-inflammatory signaling pathway, and the PI3K\u2212Akt signaling pathway are three notable pathways involved in affecting ovarian reserve capacity according to bioinformatics analysis. In addition, the concentration of estradiol on the hCG day was slightly but positively correlated with OSM (\n                      <jats:italic>r<\/jats:italic>\n                      =0.457,\n                      <jats:italic>P<\/jats:italic>\n                      =0.029). A significantly greater level of OSM (5.41 \u00b1 2.65 vs. 3.94 \u00b1 1.23 pg\/mL,\n                      <jats:italic>P<\/jats:italic>\n                      =0.007) was detected in the serum of NOR patients via ELISA verification, and the sensitivity and specificity of ovarian reserve division were 50.00% and 83.33%, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study proposed that immunological changes assessed by PEA technology affect ovarian function in humans and that OSM may serve as a potential inflammatory biomarker for ovarian function in serum, thus revealing alterations in FF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1525392","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:16:55Z","timestamp":1739146615000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Proximity extension assay revealed novel inflammatory biomarkers for follicular development and ovarian function: a prospective controlled study combining serum and follicular fluid"],"prefix":"10.3389","volume":"16","author":[{"given":"Chong","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianhua","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangjuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,10]]},"reference":[{"key":"B1","article-title":"Ovarian IL-1\u03b1 and IL-1\u03b2 levels are associated with primary ovarian insufficiency","volume":"11","author":"Yang","year":"2018","journal-title":"Int J Clin Exp Pathol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e13292","DOI":"10.1111\/aji.13292","article-title":"Dysregulated cytokine profile associated with biochemical premature ovarian insufficiency","volume":"84","author":"Liu","year":"2020","journal-title":"Am J Reprod Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-019-01497-8","article-title":"Chronically elevated androgen and\/or consumption of a Western-style diet impairs oocyte quality and granulosa cell function in the nonhuman primate periovulatory follicle","volume":"36","author":"Bishop","year":"2019","journal-title":"J Assist Reprod Genet"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-011-1251-1","article-title":"Vascular endothelial growth factor-A(165) (VEGF-A(165)) stimulates the in vitro development and oocyte competence of goat preantral follicles","volume":"346","author":"Ara\u00fajo","year":"2011","journal-title":"Cell Tissue Res"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2019.154876","article-title":"Serum biomarker analysis in patients with premature ovarian insufficiency","volume":"126","author":"Liu","year":"2020","journal-title":"Cytokine"},{"key":"B6","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1002\/mrd.23631","article-title":"RNA-sequencing reveals genes linked with oocyte developmental potential in bovine cumulus cells","volume":"89","author":"Mart\u00ednez-Moro","year":"2022","journal-title":"Mol Reprod Dev"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.628473","article-title":"The inflammasome contributes to depletion of the ovarian reserve during aging in mice","volume":"8","author":"Lliberos","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.72889","article-title":"Inactivation of Exosc10 in the oocyte impairs oocyte development and maturation, leading to a depletion of the ovarian reserve in mice","volume":"19","author":"Demini","year":"2023","journal-title":"Int J Biol Sci"},{"key":"B9","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/s42003-019-0464-9","article-title":"High throughput proteomics identifies a high-accuracy 11 plasma protein biomarker signature for ovarian cancer","volume":"2","author":"Enroth","year":"2019","journal-title":"Commun Biol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2493","DOI":"10.1038\/s41467-021-22767-z","article-title":"Next generation plasma proteome profiling to monitor health and disease","volume":"12","author":"Zhong","year":"2021","journal-title":"Nat Commun"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/del257","article-title":"Peptide and protein profiles in serum and follicular fluid of women undergoing IVF","volume":"21","author":"Schweigert","year":"2006","journal-title":"Hum Reprod"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0238520","article-title":"Serum IL-1RA levels increase from follicular to luteal phase of the ovarian cycle: A pilot study on human female immune responses","volume":"15","author":"Vetrano","year":"2020","journal-title":"PloS One"},{"key":"B13","article-title":"Serum retinol-binding protein-4 levels in polycystic ovary syndrome patients undergoing controlled ovarian hyperstimulation for in-vitro fertilization cycle","volume":"37","author":"Orvieto","year":"2010","journal-title":"Clin Exp Obstet Gynecol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr424","article-title":"Homogeneous antibody-based proximity extension assays provide sensitive and specific detection of low-abundant proteins in human blood","volume":"39","author":"Lundberg","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0157197","article-title":"Axin-1 regulates meiotic spindle organization in mouse oocytes","volume":"11","author":"He","year":"2016","journal-title":"PloS One"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23095013","article-title":"SIRT2 is critical for sheep oocyte maturation through regulating function of surrounding granulosa cells","volume":"23","author":"Fang","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1210\/me.2006-0028","article-title":"Intraovarian tumor necrosis factor-related weak inducer of apoptosis\/fibroblast growth factor-inducible-14 ligand-receptor system limits ovarian preovulatory follicles from excessive luteinization","volume":"20","author":"De","year":"2006","journal-title":"Mol Endocrinol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1186\/s13048-023-01293-0","article-title":"Oxidative stress and inflammatory markers in ovarian follicular fluid of women with diminished ovarian reserve during in vitro fertilization","volume":"16","author":"Huang","year":"2023","journal-title":"J Ovarian Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2016.02.005","article-title":"A new more detailed stratification of low responders to ovarian stimulation: from a poor ovarian response to a low prognosis concept","volume":"105","author":"Alviggi","year":"2016","journal-title":"Fertil Steril"},{"key":"B20","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s12014-018-9216-y","article-title":"A two-step strategy for identification of plasma protein biomarkers for endometrial and ovarian cancer","volume":"15","author":"Enroth","year":"2018","journal-title":"Clin Proteomics"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2023.1185021","article-title":"Olink proteomics profiling platform reveals non-invasive inflammatory related protein biomarkers in autism spectrum disorder","volume":"16","author":"Bao","year":"2023","journal-title":"Front Mol Neurosci"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/imt2.175","article-title":"Wekemo Bioincloud: A user-friendly platform for meta-omics data analyses","volume":"3","author":"Gao","year":"2024","journal-title":"Imeta"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deaa335","article-title":"Proteome of fluid from human ovarian small antral follicles reveals insights in folliculogenesis and oocyte maturation","volume":"36","author":"Pla","year":"2021","journal-title":"Hum Reprod"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.830691","article-title":"Proteomic analysis of the alterations in follicular fluid proteins during oocyte maturation in humans","volume":"12","author":"Wang","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jevs.2021.103724","article-title":"Influence of reproductive status on equine serum proteome: preliminary results","volume":"105","author":"Pennington","year":"2021","journal-title":"J Equine Vet Sci"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2017.1295178","article-title":"Regulation of 4E-BP1 activity in the mammalian oocyte","volume":"16","author":"Jansova","year":"2017","journal-title":"Cell Cycle"},{"key":"B27","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.theriogenology.2021.01.008","article-title":"In vitro maturation on ovarian granulosa cells encapsulated in agarose matrix improves developmental competence of porcine oocytes","volume":"164","author":"Park","year":"2021","journal-title":"Theriogenology"},{"key":"B28","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.theriogenology.2020.03.013","article-title":"Developmental potential of buffalo embryos cultured in serum free culture system","volume":"149","author":"Shahzad","year":"2020","journal-title":"Theriogenology"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00578","article-title":"Maternal cytokines CXCL12, VEGFA, and WNT5A promote porcine oocyte maturation via MAPK activation and canonical WNT inhibition","volume":"8","author":"Liu","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.domaniend.2014.06.002","article-title":"Vascular endothelial growth factor A improves quality of matured porcine oocytes and developing parthenotes","volume":"49","author":"Kere","year":"2014","journal-title":"Domest Anim Endocrinol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1097\/AOG.0000000000004171","article-title":"Circulating vascular endothelial growth factor and soluble fms-like tyrosine kinase-1 as biomarkers for endometrial remodeling across the menstrual cycle","volume":"137","author":"Zolton","year":"2021","journal-title":"Obstet Gynecol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1282694","article-title":"Gut microbiota and metabolites in estrus cycle and their changes in a menopausal transition rat model with typical neuroendocrine aging","volume":"14","author":"Dai","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2004.10.043","article-title":"Immunocytochemical detection and reverse transcription polymerase chain reaction expression of oncostatin M (OSM) and its receptor (OSM-Rbeta) in human fetal and adult ovaries","author":"Abir","year":"2005","journal-title":"Fertil Steril"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-24-0140","article-title":"Oncostatin M: friend or foe in PCOS pathogenesis","volume":"263","author":"Nikanfar","year":"2024","journal-title":"J Endocrinol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1239732","article-title":"The clinical relevance of OSM in inflammatory diseases: a comprehensive review","volume":"14","author":"Wolf","year":"2023","journal-title":"Front Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.repbio.2022.100633","article-title":"Oncostatin M and its receptor in women with polycystic ovary syndrome and association with assisted reproductive technology outcomes","volume":"22","author":"Nikanfar","year":"2022","journal-title":"Reprod Biol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3390\/life12081247","article-title":"Rescue IVM of denuded GV- and MI-stage oocytes of premenopausal rats with oncostatin M, insulin-like growth factor I, and growth hormone","volume":"12","author":"Akdemir","year":"2022","journal-title":"Life (Basel)"},{"key":"B38","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1186\/s13048-024-01525-x","article-title":"Causal relationship between inflammatory cytokines and polycystic ovary syndrome: a bidirectional mendelian randomization study","volume":"17","author":"Tian","year":"2024","journal-title":"J Ovarian Res"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231911096","article-title":"OSM\/OSMR and interleukin 6 family cytokines in physiological and pathological condition","volume":"23","author":"Lantieri","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B40","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1186\/s13104-024-06988-1","article-title":"Multi-locus high-risk alleles association from interleukin\u2019s genes with female infertility and certain comorbidities","volume":"17","author":"Khashei Varnamkhasti","year":"2024","journal-title":"BMC Res Notes"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2023.1154067","article-title":"Whole exome sequencing reveals novel variants associated with diminished ovarian reserve in young women","volume":"14","author":"Li","year":"2023","journal-title":"Front Genet"},{"key":"B42","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s12958-022-00926-1","article-title":"Comparative analyses in transcriptome of human granulosa cells and follicular fluid micro-environment between poor ovarian responders with conventional controlled ovarian or mild ovarian stimulations","volume":"20","author":"Liu","year":"2022","journal-title":"Reprod Biol Endocrinol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1186\/s13048-023-01272-5","article-title":"The causal association between systemic inflammatory regulators and primary ovarian insufficiency: a bidirectional mendelian randomization study","volume":"16","author":"Wang","year":"2023","journal-title":"J Ovarian Res"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.22190","article-title":"Recombinant human follicle-stimulating hormone and transforming growth factor-alpha enhance in vitro maturation of porcine oocytes","volume":"80","author":"Mito","year":"2013","journal-title":"Mol Reprod Dev"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1080\/01478885.2022.2109883","article-title":"Determination of mTOR signal pathway in MMTV-TGF\u03b1 mice ovary at different ages","volume":"46","author":"Onel","year":"2023","journal-title":"J Histotechnol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1186\/s13287-020-01904-3","article-title":"hUMSCs regulate the differentiation of ovarian stromal cells via TGF-\u03b21\/Smad3 signaling pathway to inhibit ovarian fibrosis to repair ovarian function in POI rats","volume":"11","author":"Cui","year":"2020","journal-title":"Stem Cell Res Ther"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1186\/s13048-023-01214-1","article-title":"Amniotic fluid-derived exosomes attenuated fibrotic changes in POI rats through modulation of the TGF-\u03b2\/Smads signaling pathway","volume":"16","author":"Nazdikbin Yamchi","year":"2023","journal-title":"J Ovarian Res"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1525392\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:16:59Z","timestamp":1739146619000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1525392\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,10]]},"references-count":47,"alternative-id":["10.3389\/fendo.2025.1525392"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1525392","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,10]]},"article-number":"1525392"}}