{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T06:42:17Z","timestamp":1784097737028,"version":"3.55.0"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Molecular Recognition"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Unexplained recurrent spontaneous abortion (URSA) remains a prevalent obstetric issue, the underlying causes of which are still not fully understood. MicroRNAs (miRNAs) have the potential to influence URSA through their regulation of gene expression. This study aimed to screen key miRNAs and to verify their regulatory roles and potential molecular mechanisms in URSA. Differentially expressed miRNAs and mRNAs in URSA were identified using GEO datasets (GSE178619 and GSE113790). Weighted gene co\u2010expression network analysis (WGCNA) was performed to identify hub miRNAs and mRNAs, followed by construction of a miRNA\u2013mRNA interaction network. Functional enrichment was analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. An oxidized low\u2010density lipoprotein (OX\u2010LDL)\u2010induced trophoblast cell model was established after concentration screening, and gain\u2010 and loss\u2010of\u2010function experiments involving miR\u2010146a\/b\u20105p and IRAK1 were conducted to evaluate cellular functions. The targeting relationship between miR\u2010146a\/b\u20105p and IRAK1 was examined using dual\u2010luciferase reporter assays. In\u00a0vivo, a URSA mouse model was constructed, and lentiviral overexpression of miR\u2010146a\/b\u20105p was applied to assess pregnancy outcomes and NF\u2010\u03baB pathway\u2010related molecular changes. Results showed that GSE178619 identified 34 differentially expressed miRNAs, while GSE113790 revealed 1056 differentially expressed mRNAs. WGCNA highlighted the MEbrown module (112 hub miRNAs) and the MEdarkorange module (673 hub mRNAs) as closely associated with URSA. Eighteen core miRNAs, including miR\u2010146a\/b\u20105p, and 21 core genes, including IRAK1, were identified, with IRAK1 upregulated in URSA and linked to the NF\u2010\u03baB signaling pathway. In\u00a0vitro, OX\u2010LDL treatment impaired trophoblast cell proliferation and invasion, promoted apoptosis and oxidative stress, reduced miR\u2010146a\/b\u20105p expression, and activated NF\u2010\u03baB signaling through IRAK1. Overexpression of miR\u2010146a\/b\u20105p alleviated these alterations, whereas inhibition of miR\u2010146a\/b\u20105p produced opposite effects that were partially reversed by IRAK1 knockdown. In URSA mice, miR\u2010146a\/b\u20105p overexpression improved pregnancy outcomes, alleviated placental pathological changes, reduced IRAK1 expression, and attenuated NF\u2010\u03baB pathway activation. Together, miR\u2010146a\/b\u20105p regulates URSA progression by targeting IRAK1 and modulating the NF\u2010\u03baB signaling pathway, suggesting its potential as a therapeutic target for URSA.<\/jats:p>","DOI":"10.1002\/jmr.70030","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T01:35:59Z","timestamp":1773279359000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>miR<\/scp>\n                    \u2010146a\/b\u20105p\u2010\n                    <scp>IRAK1<\/scp>\n                    \u2010\n                    <scp>NF<\/scp>\n                    \u2010\n                    <scp>\u03baB<\/scp>\n                    Axis Regulates Unexplained Recurrent Spontaneous Abortion"],"prefix":"10.1002","volume":"39","author":[{"given":"Fengping","family":"He","sequence":"first","affiliation":[{"name":"Institute of Reproduction and Genetics Dongguan Maternal and Child Health Care Hospital  Dongguan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shushu","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Genetics Center Yubei People's Hospital  Shaoguan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lujing","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Reproduction and Genetics Dongguan Maternal and Child Health Care Hospital  Dongguan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8250-1498","authenticated-orcid":false,"given":"Jiwu","family":"Lou","sequence":"additional","affiliation":[{"name":"Institute of Reproduction and Genetics Dongguan Maternal and Child Health Care Hospital  Dongguan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenming","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Genetics Center Yubei People's Hospital  Shaoguan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Genetics Center Yubei People's Hospital  Shaoguan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tizhen","family":"Yan","sequence":"additional","affiliation":[{"name":"Institute of Reproduction and Genetics Dongguan Maternal and Child Health Care Hospital  Dongguan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8217-371X","authenticated-orcid":false,"given":"Yongmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Reproduction and Genetics Dongguan Maternal and Child Health Care Hospital  Dongguan Guangdong China"},{"name":"Department of Dean's Office Dongguan Eighth People's Hospital (Dongguan Children's Hospital)  Dongguan Guangdong 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