{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T19:19:22Z","timestamp":1793992762562,"version":"4.8.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T00:00:00Z","timestamp":1723075200000},"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. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Unexplained recurrent pregnancy loss (URPL) is a clinical dilemma in reproductive fields. Its diagnosis is mainly exclusionary after extensive clinical examination, and some of the patients may still face the risk of miscarriage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed follicular fluid (FF) from <jats:italic>in vitro<\/jats:italic> fertilization (IVF) in eight patients with URPL without endocrine abnormalities or verifiable causes of abortion and eight secondary infertility controls with no history of pregnancy loss who had experienced at least one normal pregnancy and delivery by direct data-independent acquisition (dDIA) quantitative proteomics to identify differentially expressed proteins (DEPs). In this study, bioinformatics analysis was performed using online software including g:profiler, String, and ToppGene. Cytoscape was used to construct the protein\u2013protein interaction (PPI) network, and ELISA was used for validation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the DEPs are involved in the biological processes (BP) of complement and coagulation cascades. Apolipoproteins (APOs) are key proteins in the PPI network. ELISA confirmed that APOB was low-expressed in both the FF and peripheral blood of URPL patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Dysregulation of the immune network intersecting coagulation and inflammatory response is an essential feature of URPL, and this disequilibrium exists as early as the oogenesis stage. Therefore, earlier intervention is necessary to prevent the development of URPL. Moreover, aberrant lipoprotein regulation appears to be a key factor contributing to URPL. The mechanism by which these factors are involved in the complement and coagulation cascade pathways remains to be further investigated, which also provides new candidate targets for URPL treatment.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1397633","type":"journal-article","created":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T10:19:30Z","timestamp":1723112370000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Proteomics profiling reveals lipid metabolism abnormalities during oogenesis in unexplained recurrent pregnancy loss"],"prefix":"10.3389","volume":"15","author":[{"given":"Kun","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bairong","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/hropen\/hoac045","article-title":"Reproductive outcomes following recurrent first-trimester miscarriage: a retrospective cohort study","author":"Linehan","year":"2022","journal-title":"Hum Reprod Open"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2021\/6696305","article-title":"The mechanism of traditional chinese medicine based on semi-targeted metabolomics to improve IVF outcomes in senile patients","author":"Ma","year":"2021","journal-title":"Evid Based Complement Alternat Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.3390\/s22041620","article-title":"Microfluidic point-of-care (POC) devices in early diagnosis: A review of opportunities and challenges","volume":"22","author":"Yang","year":"2022","journal-title":"Sensors"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.placenta.2017.11.001","article-title":"Proteomics and bioinformatics analysis of altered protein expression in the placental villous tissue from early recurrent miscarriage patients","volume":"61","author":"Pan","year":"2018","journal-title":"Placenta"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioab140","article-title":"Proteomic and functional analysis of proteins related to embryonic development of decidua in patients with recurrent pregnancy loss","volume":"105","author":"Xiong","year":"2021","journal-title":"Biol Reprod"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1186\/s12014-021-09312-2","article-title":"Proteomic analysis of decidua in patients with recurrent pregnancy loss (RPL) reveals mitochondrial oxidative stress dysfunction","volume":"18","author":"Yin","year":"2021","journal-title":"Clin Proteomics"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2020.1750202","article-title":"A circulating extracellular vesicles-based novel screening tool for colorectal cancer revealed by shotgun and data-independent acquisition mass spectrometry","volume":"9","author":"Zheng","year":"2020","journal-title":"J Extracell Vesicles"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201600300","article-title":"Relative protein quantification and accessible biology in lung tumor proteomes from four LC-MS\/MS discovery platforms","volume":"17","author":"Stewart","year":"2017","journal-title":"Proteomics"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.RA119.001714","article-title":"Reproducibility, specificity and accuracy of relative quantification using spectral library-based data-independent acquisition","volume":"19","author":"Barkovits","year":"2020","journal-title":"Mol Cell Proteomics"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.O115.048181","article-title":"MS1 peptide ion intensity chromatograms in MS2 (SWATH) data independent acquisitions. 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