Icariin targets PDE5A to regulate viability, DNA synthesis and DNA damage of spermatogonial stem cells and improves reproductive capacity.

Tian-Long LIAO; Cai-Mei HE; Di XIAO; Zhi-Rong ZHANG; Zuping HE; Xiao-Ping YANG

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Icariin targets PDE5A to regulate viability, DNA synthesis and DNA damage of spermatogonial stem cells and improves reproductive capacity.

Author: Tian-Long LIAO ¹ ; Cai-Mei HE ¹ ; Di XIAO ¹ ; Zhi-Rong ZHANG ¹ ; Zuping HE ¹ ; Xiao-Ping YANG ¹
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1. 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.
Publication Type:Journal Article
Keywords: DNA damage; Icariin; PDE5A; proliferation; spermatogonial stem cells
MeSH: Male; Animals; Flavonoids/pharmacology*; Mice; Cyclic Nucleotide Phosphodiesterases, Type 5/drug effects*; DNA Damage/drug effects*; Cell Survival/drug effects*; Cell Proliferation/drug effects*; Spermatogonia/drug effects*; Reproduction/drug effects*; Adult Germline Stem Cells/metabolism*; DNA Replication/drug effects*
From: Asian Journal of Andrology 2025;27(4):543-549
CountryChina
Language:English
Abstract: 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 2 O 2 ) 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 2 O 2 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.