{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T19:30:07Z","timestamp":1777145407608,"version":"3.51.4"},"reference-count":42,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"crossref","award":["2020J01986"],"award-info":[{"award-number":["2020J01986"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"crossref","award":["2021J01236"],"award-info":[{"award-number":["2021J01236"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fujian Provincial Finance Project","award":["BPB-2023WJB1243"],"award-info":[{"award-number":["BPB-2023WJB1243"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n               <jats:title>Background<\/jats:title>\n               <jats:p>Unexplained recurrent spontaneous abortion (URSA) is a complex pregnancy complication with a high miscarriage rate. Incomprehensive understanding of the molecular mechanism in URSA also leads to a lack of effective treatment methods. Hence, the current study aimed to explore the underlying pathogenesis of URSA applying metabonomic and bioinformatics analysis.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Methods<\/jats:title>\n               <jats:p>The decidual tissues of eight URSA samples and eight normal pregnancy (normal control, NC) samples were collected for liquid chromatography-mass spectrometry (LC-MS) analysis using the Progenesis QI metabolomics software. The orthogonal partial least squares discrimination analysis (OPLS-DA) and the Human Metabolome Database (HMDB) were employed for differential metabolite analysis and pathway enrichment analysis, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway topological analysis was performed to rank the importance of pathways involved in URSA, and differential proteins were identified based on fold change difference. Finally, a metabolic network was visualized by the Cytoscape tool.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Results<\/jats:title>\n               <jats:p>After LC-MS analysis and quality control, samples in the same group showed high consistency and reliability. Differential metabolites between NC and URSA groups were mainly enriched to five biological processes, with glycerophospholipid metabolism pathway containing the greatest number of differential metabolites. KEGG enrichment analysis showed significant differences in glycerophospholipid metabolism, bile secretion, and choline metabolism pathways, with glycerophospholipid metabolism showing a higher pathway importance. Proteome and metabolome analysis revealed a total of 65 overlapping pathways involved in the differential proteins and differential metabolites, and finally <jats:italic>PLD1<\/jats:italic>, <jats:italic>CHPT1<\/jats:italic> and <jats:italic>PLA2G2A<\/jats:italic> were identified as the key genes in glycerophospholipid metabolism pathway.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Conclusion<\/jats:title>\n               <jats:p>LC-MS analysis revealed that glycerophospholipid metabolism pathway and its three key genes were crucially involved in URSA progression, providing novel insights into the treatment strategy of URSA.<\/jats:p>\n            <\/jats:sec>","DOI":"10.7717\/peerj.19317","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T08:33:56Z","timestamp":1746002036000},"page":"e19317","source":"Crossref","is-referenced-by-count":3,"title":["Metabolomics and proteomics analyses reveal the role of the glycerophospholipid metabolism pathway in unexplained recurrent spontaneous abortion"],"prefix":"10.7717","volume":"13","author":[{"given":"Yihong","family":"Chen","sequence":"first","affiliation":[{"name":"College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Department of Obstetrics and Gynecology, Fujian Maternity and Child Health Hospital, Fujian Clinical Research Center for Maternal-Fetal Medicine, Fuzhou, China"},{"name":"Department of Obstetrics and Gynecology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiumei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bei","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leiyi","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juanbing","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianying","family":"Yan","sequence":"additional","affiliation":[{"name":"College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Department of Obstetrics and Gynecology, Fujian Maternity and Child Health Hospital, Fujian Clinical Research Center for Maternal-Fetal Medicine, Fuzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4443","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"issue":"6","key":"10.7717\/peerj.19317\/ref-1","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1097\/OGX.0b013e31828aca19","article-title":"Current concepts and new trends in the diagnosis and management of recurrent miscarriage","volume":"68","author":"Alijotas-Reig","year":"2013","journal-title":"Obstetrical & Gynecological Survey"},{"issue":"6","key":"10.7717\/peerj.19317\/ref-2","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.medcli.2014.01.033","article-title":"Regulatory T cells maternal-foetal immune tolerance and recurrent miscarriage: new therapeutic challenging opportunities","volume":"144","author":"Alijotas-Reig","year":"2015","journal-title":"Medicina Clinica"},{"issue":"11","key":"10.7717\/peerj.19317\/ref-3","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.1016\/j.bbalip.2016.08.002","article-title":"Structural and functional basis of phospholipid oxygenase activity of bacterial lipoxygenase from Pseudomonas aeruginosa","volume":"1861","author":"Banthiya","year":"2016","journal-title":"Biochimica et Biophysica Acta"},{"issue":"2","key":"10.7717\/peerj.19317\/ref-4","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/s00281-007-0069-0","article-title":"The Th1\/Th2 paradigm: still important in pregnancy?","volume":"29","author":"Chaouat","year":"2007","journal-title":"Seminars in Immunopathology"},{"issue":"7","key":"10.7717\/peerj.19317\/ref-5","doi-asserted-by":"publisher","first-page":"3738","DOI":"10.1073\/pnas.1916588117","article-title":"NAD deficiency due to environmental factors or gene-environment interactions causes congenital malformations and miscarriage in mice","volume":"117","author":"Cuny","year":"2020","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"1","key":"10.7717\/peerj.19317\/ref-6","doi-asserted-by":"publisher","first-page":"17009","DOI":"10.1289\/EHP10477","article-title":"BPDE, the migration and invasion of human trophoblast cells, and occurrence of miscarriage in humans: roles of a novel lncRNA-HZ09","volume":"131","author":"Dai","year":"2023","journal-title":"Environmental Health Perspectives"},{"issue":"1","key":"10.7717\/peerj.19317\/ref-7","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s12916-021-02227-7","article-title":"Chromosomally normal miscarriage is associated with vaginal dysbiosis and local inflammation","volume":"20","author":"Grewal","year":"2022","journal-title":"BMC Medicine"},{"key":"10.7717\/peerj.19317\/ref-8","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/1471-2105-14-7","article-title":"GSVA: gene set variation analysis for microarray and RNA-seq data","volume":"14","author":"H\u00e4nzelmann","year":"2013","journal-title":"BMC Bioinformatics"},{"issue":"2","key":"10.7717\/peerj.19317\/ref-9","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1093\/biolre\/ioab101","article-title":"Multi-omics reveals a relationship between endometrial amino acid metabolism and autophagy in women with recurrent miscarriage\u2020","volume":"105","author":"Hong","year":"2021","journal-title":"Biology of Reproduction"},{"issue":"6","key":"10.7717\/peerj.19317\/ref-10","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.3390\/foods12061162","article-title":"Using OPLS-DA to fingerprint key free amino and fatty acids in understanding the influence of high pressure processing in New Zealand clams","volume":"12","author":"How","year":"2023","journal-title":"Foods"},{"issue":"19\u201320","key":"10.7717\/peerj.19317\/ref-11","doi-asserted-by":"publisher","first-page":"2305","DOI":"10.1007\/s00018-005-5195-z","article-title":"Phospholipase D: a lipid centric review","volume":"62","author":"Jenkins","year":"2005","journal-title":"Cellular and Molecular Life Sciences: CMLS"},{"issue":"1","key":"10.7717\/peerj.19317\/ref-12","doi-asserted-by":"publisher","first-page":"39","DOI":"10.3109\/10409238.2012.735644","article-title":"Mechanism of the ABC transporter ATPase domains: catalytic models and the biochemical and biophysical record","volume":"48","author":"Jones","year":"2013","journal-title":"Critical Reviews in Biochemistry and Molecular Biology"},{"issue":"7","key":"10.7717\/peerj.19317\/ref-13","doi-asserted-by":"publisher","first-page":"4085","DOI":"10.4049\/jimmunol.0803769","article-title":"Vascular endothelial growth factor C facilitates immune tolerance and endovascular activity of human uterine NK cells at the maternal-fetal interface","volume":"182","author":"Kalkunte","year":"2009","journal-title":"Journal of Immunology"},{"issue":"3","key":"10.7717\/peerj.19317\/ref-14","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1155\/1991\/83493","article-title":"CD3- leukocytes present in the human uterus during early placentation: phenotypic and morphologic characterization of the CD56++ population","volume":"1","author":"King","year":"1991","journal-title":"Developmental Immunology"},{"issue":"5","key":"10.7717\/peerj.19317\/ref-15","doi-asserted-by":"publisher","first-page":"2346","DOI":"10.1021\/acs.jproteome.9b00082","article-title":"Evosep one enables robust deep proteome coverage using tandem mass tags while significantly reducing instrument time","volume":"18","author":"Krieger","year":"2019","journal-title":"Journal of Proteome Research"},{"issue":"1","key":"10.7717\/peerj.19317\/ref-16","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.ogc.2013.10.004","article-title":"Antiphospholipid antibody syndrome","volume":"41","author":"Kutteh","year":"2014","journal-title":"Obstetrics and Gynecology Clinics of North America"},{"issue":"3","key":"10.7717\/peerj.19317\/ref-17","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1016\/j.gendis.2019.06.003","article-title":"CircRNA expression profiles in decidual tissue of patients with early recurrent miscarriage","volume":"7","author":"Li","year":"2020","journal-title":"Genes & Diseases"},{"issue":"6","key":"10.7717\/peerj.19317\/ref-18","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1111\/jog.12647","article-title":"Decreased \u03b2-catenin expression in first-trimester villi and decidua of patients with recurrent spontaneous abortion","volume":"41","author":"Li","year":"2015","journal-title":"The Journal of Obstetrics and Gynaecology Research"},{"issue":"5","key":"10.7717\/peerj.19317\/ref-19","doi-asserted-by":"publisher","first-page":"100750","DOI":"10.1016\/j.mcpro.2024.100750","article-title":"An automated and fast sample preparation workflow for laser microdissection guided ultrasensitive proteomics","volume":"23","author":"Makhmut","year":"2024","journal-title":"Molecular & Cellular Proteomics: MCP"},{"issue":"1","key":"10.7717\/peerj.19317\/ref-20","doi-asserted-by":"publisher","first-page":"65","DOI":"10.32604\/biocell.2023.045986","article-title":"Review on analytical technologies and applications in metabolomics","volume":"48","author":"Meng","year":"2024","journal-title":"Biocell"},{"issue":"2","key":"10.7717\/peerj.19317\/ref-21","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1111\/j.1538-7836.2006.01753.x","article-title":"International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS)","volume":"4","author":"Miyakis","year":"2006","journal-title":"Journal of Thrombosis and Haemostasis: JTH"},{"issue":"4","key":"10.7717\/peerj.19317\/ref-22","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1016\/j.bbabio.2013.10.006","article-title":"Functional role of cardiolipin in mitochondrial bioenergetics","volume":"1837","author":"Paradies","year":"2014","journal-title":"Biochimica et Biophysica Acta"},{"issue":"1","key":"10.7717\/peerj.19317\/ref-23","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.fertnstert.2012.09.023","article-title":"Definitions of infertility and recurrent pregnancy loss: a committee opinion","volume":"99","author":"Practice Committee of the American Society for Reproductive Medicine","year":"2013","journal-title":"Fertility and Sterility"},{"issue":"12","key":"10.7717\/peerj.19317\/ref-24","doi-asserted-by":"publisher","first-page":"1842","DOI":"10.1080\/15384101.2015.1033593","article-title":"Involvement of atypical transcription factor E2F8 in the polyploidization during mouse and human decidualization","volume":"14","author":"Qi","year":"2015","journal-title":"Cell Cycle"},{"issue":"4","key":"10.7717\/peerj.19317\/ref-25","doi-asserted-by":"publisher","first-page":"547","DOI":"10.32604\/oncologie.2021.019738","article-title":"In vivo effects of aqueous extract of Gongronema latifolium benth on the tumor necrosis factor-\u03b1, transforming growth factor-\u03b2, and hepatic enzymes","volume":"23","author":"Rowaiye","year":"2021","journal-title":"Oncologie"},{"key":"10.7717\/peerj.19317\/ref-26","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.jri.2017.09.007","article-title":"Antiphospholipid syndrome and recurrent miscarriage: a systematic review and meta-analysis","volume":"123","author":"Santos","year":"2017","journal-title":"Journal of Reproductive Immunology"},{"issue":"6","key":"10.7717\/peerj.19317\/ref-27","doi-asserted-by":"publisher","first-page":"693","DOI":"10.32604\/chd.2024.048081","article-title":"CHDTEPDB: transcriptome expression profile database and interactive analysis platform for congenital heart disease","volume":"18","author":"Song","year":"2023"},{"key":"10.7717\/peerj.19317\/ref-28","doi-asserted-by":"publisher","first-page":"463122","DOI":"10.1016\/j.chroma.2022.463122","article-title":"Zwitter-ionic monolith-based spintip column coupled with Evosep One liquid chromatography for high-throughput proteomic analysis","volume":"1675","author":"Su","year":"2022","journal-title":"Journal of Chromatography A"},{"issue":"8","key":"10.7717\/peerj.19317\/ref-29","doi-asserted-by":"publisher","first-page":"5082","DOI":"10.4049\/jimmunol.179.8.5082","article-title":"Modulation of miR-155 and miR-125b levels following lipopolysaccharide\/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock","volume":"179","author":"Tili","year":"2007","journal-title":"Journal of Immunology"},{"issue":"7","key":"10.7717\/peerj.19317\/ref-30","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1194\/jlr.R700020-JLR200","article-title":"Phosphatidylserine and phosphatidylethanolamine in mammalian cells: two metabolically related aminophospholipids","volume":"49","author":"Vance","year":"2008","journal-title":"Journal of Lipid Research"},{"key":"10.7717\/peerj.19317\/ref-31","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.placenta.2021.07.001","article-title":"The metabolic landscape of decidua in recurrent pregnancy loss using a global metabolomics approach","volume":"112","author":"Wang","year":"2021","journal-title":"Placenta"},{"issue":"3","key":"10.7717\/peerj.19317\/ref-32","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1007\/s10565-021-09646-5","article-title":"Integrated lipidomic and transcriptomic analysis reveals clarithromycin-induced alteration of glycerophospholipid metabolism in the cerebral cortex of mice","volume":"39","author":"Wang","year":"2023","journal-title":"Cell Biology and Toxicology"},{"issue":"2","key":"10.7717\/peerj.19317\/ref-33","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1007\/s00005-012-0161-6","article-title":"Immunotherapy of patients with recurrent spontaneous miscarriage and idiopathic infertility: does the immunization-dependent Th2 cytokine overbalance really matter?","volume":"60","author":"Wilczy\u0144ski","year":"2012","journal-title":"Archivum Immunologiae Et Therapiae Experimentalis"},{"key":"10.7717\/peerj.19317\/ref-34","article-title":"Effect of pregnancy on lipid metabolism and lipoprotein levels","volume-title":"Endotext","author":"Wild","year":"2000"},{"issue":"6","key":"10.7717\/peerj.19317\/ref-35","first-page":"8812","article-title":"Soluble costimulatory molecule sTim3 regulates the differentiation of Th1 and Th2 in patients with unexplained recurrent spontaneous abortion","volume":"8","author":"Wu","year":"2015","journal-title":"International Journal of Clinical and Experimental Medicine"},{"issue":"18","key":"10.7717\/peerj.19317\/ref-36","doi-asserted-by":"publisher","first-page":"2342","DOI":"10.1093\/bioinformatics\/btq418","article-title":"MetPA: a web-based metabolomics tool for pathway analysis and visualization","volume":"26","author":"Xia","year":"2010","journal-title":"Bioinformatics"},{"issue":"10","key":"10.7717\/peerj.19317\/ref-37","doi-asserted-by":"publisher","first-page":"2459","DOI":"10.1080\/15548627.2022.2039000","article-title":"A defective lysophosphatidic acid-autophagy axis increases miscarriage risk by restricting decidual macrophage residence","volume":"18","author":"Yang","year":"2022","journal-title":"Autophagy"},{"issue":"1","key":"10.7717\/peerj.19317\/ref-38","doi-asserted-by":"publisher","first-page":"199","DOI":"10.3390\/ijms23010199","article-title":"Regulation and function of laminin A5 during mouse and human decidualization","volume":"23","author":"Yang","year":"2021","journal-title":"International Journal of Molecular Sciences"},{"issue":"1","key":"10.7717\/peerj.19317\/ref-39","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1159\/000459633","article-title":"Metabolic adaptations in pregnancy: a review","volume":"70","author":"Zeng","year":"2017","journal-title":"Annals of Nutrition & Metabolism"},{"issue":"19","key":"10.7717\/peerj.19317\/ref-40","doi-asserted-by":"publisher","first-page":"11721","DOI":"10.3390\/ijms231911721","article-title":"PLA2G2A phospholipase promotes fatty acid synthesis and energy metabolism in pancreatic cancer cells with K-ras mutation","volume":"23","author":"Zhang","year":"2022","journal-title":"International Journal of Molecular Sciences"},{"issue":"3","key":"10.7717\/peerj.19317\/ref-41","doi-asserted-by":"publisher","first-page":"222","DOI":"10.2174\/1573412919666221223152915","article-title":"Metabolomics-based approach to analyze the therapeutic targets andmetabolites of a synovitis ointment for knee osteoarthritis","volume":"19","author":"Zhang","year":"2023","journal-title":"Current Pharmaceutical Analysis"},{"key":"10.7717\/peerj.19317\/ref-42","doi-asserted-by":"publisher","first-page":"794938","DOI":"10.3389\/fphar.2022.794938","article-title":"Deciphering the mechanism of bushen huoxue decotion on decidualization by intervening autophagy via AMPK\/mTOR\/ULK1: a novel discovery for URSA treatment","volume":"13","author":"Zhao","year":"2022","journal-title":"Frontiers in Pharmacology"}],"container-title":["PeerJ"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/peerj.com\/articles\/19317.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/19317.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/19317.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/19317.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T08:34:17Z","timestamp":1746002057000},"score":1,"resource":{"primary":{"URL":"https:\/\/peerj.com\/articles\/19317"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,30]]},"references-count":42,"alternative-id":["10.7717\/peerj.19317"],"URL":"https:\/\/doi.org\/10.7717\/peerj.19317","archive":["CLOCKSS","LOCKSS","Portico"],"relation":{},"ISSN":["2167-8359"],"issn-type":[{"value":"2167-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,30]]},"article-number":"e19317"}}