{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:40:42Z","timestamp":1791916842027,"version":"4.3.4"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Icariin is a pure compound derived from Epimedium brevicornu Maxim, and it helps the regulation of male reproduction. Nevertheless, the role and underlying mechanisms of Icariin in mediating male germ cell development remain to be clarified. Here, we have demonstrated that Icariin promoted proliferation and DNA synthesis of mouse spermatogonial stem cells (SSCs). Furthermore, surface plasmon resonance iron (SPRi) and molecular docking (MOE) assays revealed that phosphodiesterase 5A (PDE5A) was an important target of Icariin in mouse SSCs. Mechanically, Icariin decreased the expression level of PDE5A. Interestingly, hydrogen peroxides (H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ) enhanced the expression level of phosphorylation H2A.X (p-H2A.X), whereas Icariin diminished the expression level of p-H2A.X and DNA damage caused by H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    in mouse SSCs. Finally, our in vivo animal study indicated that Icariin protected male reproduction. Collectively, these results implicate that Icariin targets PDE5A to regulate mouse SSC viability and DNA damage and improves male reproductive capacity. This study thus sheds new insights into molecular mechanisms underlying the fate decisions of mammalian SSCs and offers a scientific basis for the clinical application of Icariin in male reproduction.\n                  <\/jats:p>","DOI":"10.4103\/aja2024106","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T10:50:35Z","timestamp":1736247035000},"page":"543-549","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":3,"title":["Icariin targets PDE5A to regulate viability, DNA synthesis and DNA damage of spermatogonial stem cells and improves reproductive capacity"],"prefix":"10.4103","volume":"27","author":[{"given":"Tian-Long","family":"Liao","sequence":"first","affiliation":[{"name":"Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, The Key Laboratory of Model Animals and Stem cell Biology in Hunan Province, The Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University School of Medicine, Changsha 410013, China"},{"name":"Department of Cardiology, Zhuzhou Hospital, The Affiliated Hospital of Xiangya Medical College of Central South University, Zhuzhou 412001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cai-Mei","family":"He","sequence":"additional","affiliation":[{"name":"Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, The Key Laboratory of Model Animals and Stem cell Biology in Hunan Province, The Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University School of Medicine, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Xiao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, The Key Laboratory of Model Animals and Stem cell Biology in Hunan Province, The Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University School of Medicine, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Rong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, The Key Laboratory of Model Animals and Stem cell Biology in Hunan Province, The Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University School of Medicine, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuping","family":"He","sequence":"additional","affiliation":[{"name":"Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, The Key Laboratory of Model Animals and Stem cell Biology in Hunan Province, The Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University School of Medicine, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ping","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, The Key Laboratory of Model Animals and Stem cell Biology in Hunan Province, The Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University School of Medicine, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,1,7]]},"reference":[{"key":"R1-20250716","first-page":"e18","volume":"103","year":"2015","journal-title":"Fertil Steril"},{"key":"R2-20250716","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1093\/humupd\/dmx022","article-title":"Temporal trends in sperm count:a systematic review and meta-regression 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