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A total of 52 chemical ingredients were identified from WZYZD. HE and TUNEL staining demonstrated that WZYZD can markedly alleviate OLI. Immunofluorescence analysis showed that WZYZD can significantly increase the expression levels of DNMT3\u2005A, PIWIL1, SETDB1, and PRMT5. Methyl capture sequencing proved that WZYZD can markedly upregulate the methylated level of <jats:italic>Spata<\/jats:italic>, <jats:italic>Bcl<\/jats:italic>, and <jats:italic>Pik3<\/jats:italic> series genes. Network pharmacology analysis proved that WZYZD can ameliorate OLI through BCL\u20102 and PI3\u2005K\u2010AKT signaling pathways. The immunofluorescence assay of BCL\u20102 and SPATA18 proved the aforementioned results. The potential mechanism of WZYZD in treating OLI mainly involved recruiting methyltransferase DNMT3\u2005A, PIWIL1, PRMT5, and SETDB1 and increasing the methylation degree of <jats:italic>Spata<\/jats:italic>, <jats:italic>Bcl<\/jats:italic>, and <jats:italic>Pik3<\/jats:italic> series genes.<\/jats:p>","DOI":"10.1002\/cbdv.202401984","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T15:08:20Z","timestamp":1729696100000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Wuzi Yanzong Decoction Ameliorates Oligoasthenozoospermia by Up\u2010Regulating Methyltransferase and Increasing <i>Spata<\/i>, <i>Bcl<\/i>, and <i>Pik3<\/i> Series Genes Methylation Level"],"prefix":"10.1002","volume":"22","author":[{"given":"Qiyan","family":"Lin","sequence":"first","affiliation":[{"name":"College of Biological and Pharmaceutical Engineering West Anhui University Traditional Chinese Medicine Institute of Anhui Dabie Mountain Anhui Engineering Research Center for Eco-agriculture of Traditional Chinese Medicine Generic Technology Research Center for Anhui Traditional Chinese Medicine Industry  Lu'an 237012, Anhui P. 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