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However, the molecular pathogenetic mechanisms responsible for androgen excess in PCOS remain largely unknow. While most previous studies have specifically focused on ovarian tissue, few have evaluated the role of extraovarian organs in PCOS. Here, it is found that KLF9 expression is up\u2010regulated in murine primary hepatocytes treated with DHEA. Notably, the genetic ablation of\n                    <jats:italic>Klf9<\/jats:italic>\n                    in hepatocytes significantly alleviated the progression of DHEA induced PCOS in mouse. Conversely, hepatic\n                    <jats:italic>Klf9<\/jats:italic>\n                    transgenic mice displayed a spontaneous PCOS\u2010like phenotype. Mechanistically, hepatic KLF9 is directly activated by intranuclear AR and then directly binds to the promoter of\n                    <jats:italic>Srd5a1<\/jats:italic>\n                    and the gene loci of\n                    <jats:italic>Hsd3b3<\/jats:italic>\n                    , which encode the enzyme for the conversion of DHEA to dihydrotestosterone, to promote its transcription in the liver. Overall, our study indicated that the liver plays a vital role in the development of PCOS and that hepatic KLF9 might be a potential therapeutic target for PCOS.\n                  <\/jats:p>","DOI":"10.1002\/advs.202508240","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T12:54:40Z","timestamp":1758632080000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Hepatic KLF9 Deficiency Inhibits Dehydroepiandrosterone (DHEA)\u2010Induced Polycystic Ovary Syndrome via Liver\u2010Ovary Axis"],"prefix":"10.1002","volume":"12","author":[{"given":"Jianli","family":"Song","sequence":"first","affiliation":[{"name":"Department of Reproductive Medicine General Hospital of Ningxia Medical University (The First Clinical Medical College of Ningxia Medical University) No. 804, Shengli Street Yinchuan Ningxia Hui Autonomous Region 750003 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