{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T19:56:39Z","timestamp":1787860599208,"version":"build-2784847793"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Key Fund Project of Hunan Provincial Department of Education","award":["24A0257"],"award-info":[{"award-number":["24A0257"]}]},{"name":"the Changsha Natural Science Fund Project","award":["kq2402176"],"award-info":[{"award-number":["kq2402176"]}]},{"name":"the Key Project of Hunan University of Chinese Medicine","award":["2024XJZA003"],"award-info":[{"award-number":["2024XJZA003"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81503611"],"award-info":[{"award-number":["81503611"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2025JJ50716"],"award-info":[{"award-number":["2025JJ50716"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec025\">\n<jats:title>Backgrounds<\/jats:title>\n<jats:p>Aspirin has been shown to enhance endometrial receptivity (ER) during the window of implantation in patients with polycystic ovary syndrome (PCOS). However, the underlying mechanisms remain unclear. This study aimed to elucidate the mechanisms by which aspirin improves ER through\u00a0metabolic\u00a0analysis of uterine lavage fluid.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec026\">\n<jats:title>Methods<\/jats:title>\n<jats:p>A PCOS rat model was established using letrozole. Body weight and estrous cycles were monitored, and the number of implanted embryos was assessed across groups. We evaluated endometrial ultrastructure, ovarian and endometrial histomorphometry. Serum levels of estradiol(E<jats:sub>2<\/jats:sub>) and progesterone(P)were measured. Moreover, through ultra-performance liquid chromatography-mass spectrometry, the study of uterine lavage fluid metabolites revealed the potential mechanism of action of aspirin.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec027\">\n<jats:title>Results<\/jats:title>\n<jats:p>Compared with the model group, aspirin treatment significantly increased embryo implantation rates, improved endometrial morphology and hormone levels. Metabolomic analysis identified 48 differential metabolites, among which five\u20142, 6-dihydroxypurine, gluconolactone, Oxaceprol, PC (18:1\/18:1), and PC (20:3e\/17:1)\u2014were identified as potential biomarkers for aspirin-mediated improvement of ER in PCOS rats. Pathway analysis revealed that aspirin primarily modulates the pentose phosphate pathway, arginine and proline metabolism, and glycerophospholipid metabolism.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec028\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Aspirin may enhance glucose metabolism, alleviate insulin resistance, promote angiogenesis, and improve vascular permeability and endometrial receptivity. These effects are likely mediated through the regulation of biomarkers involved in the pentose phosphate pathway, arginine and proline metabolism, and glycerophospholipid pathways in uterine lavage fluid.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0324432","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T17:44:53Z","timestamp":1747935893000},"page":"e0324432","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Exploring the mechanism of action of aspirin in improving endometrial receptivity in PCOS rats based on uterine lavage fluid metabolomics"],"prefix":"10.1371","volume":"20","author":[{"given":"Ying","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqing","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4266-1838","authenticated-orcid":true,"given":"Shuo","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,5,22]]},"reference":[{"issue":"6701","key":"pone.0324432.ref001","article-title":"Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction","volume":"384","author":"Y Liu","year":"2024","journal-title":"Science"},{"key":"pone.0324432.ref002","doi-asserted-by":"crossref","first-page":"153654","DOI":"10.1016\/j.phymed.2021.153654","article-title":"Berberine improves ovulation and endometrial receptivity in polycystic ovary syndrome","volume":"91","author":"Z Wang","year":"2021","journal-title":"Phytomedicine"},{"issue":"8","key":"pone.0324432.ref003","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/j.jogc.2021.03.018","article-title":"Aspirin for Endometrial Preparation in Patients Undergoing IVF: A Systematic Review and Meta-analysis","volume":"43","author":"A Mourad","year":"2021","journal-title":"J Obstet Gynaecol Can"},{"issue":"8","key":"pone.0324432.ref004","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.jogoh.2019.02.004","article-title":"A new look at low-dose aspirin: Co-administration with tamoxifen in ovulation induction in anovulatory PCOS women","volume":"48","author":"NK Aref","year":"2019","journal-title":"J Gynecol Obstet Hum Reprod"},{"issue":"2","key":"pone.0324432.ref005","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/ijgo.13699","article-title":"Low-dose aspirin treatment improves endometrial receptivity in the midluteal phase in unexplained recurrent implantation failure","volume":"156","author":"X Zhang","year":"2022","journal-title":"Int J Gynaecol Obstet"},{"issue":"5","key":"pone.0324432.ref006","first-page":"6337","article-title":"Transdermal estrogen gel and oral aspirin combination therapy improves fertility prognosis via the promotion of endometrial receptivity in moderate to severe intrauterine adhesion","volume":"17","author":"Y Chi","year":"2018","journal-title":"Mol Med Rep"},{"issue":"8","key":"pone.0324432.ref007","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.1093\/humrep\/deab123","article-title":"Global transcriptomic changes occur in uterine fluid-derived extracellular vesicles during the endometrial window for embryo implantation","volume":"36","author":"E Giacomini","year":"2021","journal-title":"Hum Reprod"},{"issue":"1","key":"pone.0324432.ref008","first-page":"10","article-title":"Effects of Anethum graveolens L. 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