{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T14:41:56Z","timestamp":1789137716667,"version":"build-2803163510"},"reference-count":48,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["81300484"],"award-info":[{"award-number":["81300484"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Research Initiation Program for High-level Talents of the Affiliated Hospital of Guangdong Medical University","award":["GCC2023016"],"award-info":[{"award-number":["GCC2023016"]}]},{"name":"Zhanjiang Science and Technology Special Fund Project","award":["2022A01169"],"award-info":[{"award-number":["2022A01169"]}]},{"name":"Zhanjiang Science and Technology Special Fund Project","award":["2024B01241"],"award-info":[{"award-number":["2024B01241"]}]},{"name":"Scientific Research Fund Project of Guangdong Medical University","award":["M2017014"],"award-info":[{"award-number":["M2017014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n               <jats:title>Background<\/jats:title>\n               <jats:p>Epigenetic regulation, including DNA methylation, is essential for normal embryonic development and maternal-fetal interactions. Recurrent miscarriage (RM), defined as the loss of two or more consecutive pregnancies, poses significant clinical and emotional challenges. However, the role of epigenetic alterations in RM, particularly in gametes and placental tissues, remains underexplored. This study aims to investigate global DNA methylation profiles and imprinting gene expression in the context of RM, providing insights into epigenetic mechanisms that contribute to pregnancy failure.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Methods<\/jats:title>\n               <jats:p>Genome-wide DNA methylation profiling was performed on sperm and chorionic villi from RM patients and control couples undergoing artificial abortion using the Illumina HumanMethylation 450 BeadChip platform. Genes related to differentially methylated probes (DMPs) in functionally critical genomic regions, including enhancers, promoters, and DNase hypersensitive sites (DHS), were identified and submitted to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Key imprinting genes (<jats:italic>CPA4<\/jats:italic> and <jats:italic>PRDM16<\/jats:italic>) were validated at the protein level using Western blotting.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Results<\/jats:title>\n               <jats:p>RM samples exhibited a significant increase in hypermethylated DMPs across all analyzed tissues, with villi and decidua showing the highest numbers of epigenetic changes. Enrichment analyses highlighted pathways implicated in tissue morphogenesis, immune regulation, and cell signaling, including the PI3K-Akt, TGF-beta, and Wnt signaling pathways. Among imprinting genes, <jats:italic>CPA4<\/jats:italic> and <jats:italic>PRDM16<\/jats:italic> showed distinct hypomethylation at enhancer regions, corresponding to elevated protein expression in RM villi tissues.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Conclusions<\/jats:title>\n               <jats:p>This study identifies profound epigenetic dysregulation in RM-associated tissues, emphasizing the contribution of imprinting gene methylation abnormalities to pregnancy loss. Future studies incorporating functional assays and animal models are essential to elucidate the causal roles of candidate genes in RM pathogenesis and maternal-fetal health.<\/jats:p>\n            <\/jats:sec>","DOI":"10.7717\/peerj.20125","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T08:47:31Z","timestamp":1759826851000},"page":"e20125","source":"Crossref","is-referenced-by-count":3,"title":["Comprehensive analysis of DNA methylation patterns in recurrent miscarriage: imprinted\/non-imprinted genes and their regulation across sperm and fetal-maternal tissues"],"prefix":"10.7717","volume":"13","author":[{"given":"Yanru","family":"Niu","sequence":"first","affiliation":[{"name":"Orthopaedic Research Lab, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanlan","family":"Yin","sequence":"additional","affiliation":[{"name":"Reproductive Medicine 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