Sophoraflavanone G disrupts human sperm function via impairing CatSper-mediated Ca²⁺ signaling

CatSper-mediated Ca²⁺ signaling plays a pivotal role in regulating various physiological functions in human sperm. Previous studies have indicated that several plant-derived compounds can affect sperm function by interfering with CatSper activation. Sophoraflavanone G (SFG), a naturally occurring prenylated flavanone isolated from sophora flavescens, has been shown remarkable pharmacological properties relevant to the treatment of human diseases. However, the potential deleterious effects of SFG on CatSper channel and fertilization-related physiological functions in human sperm remain unclear. Here, by utilizing population intracellular Ca²⁺ measurements, we revealed that SFG suppressed sperm Ca²⁺ entry evoked by CatSper activation. Patch-clamp recordings further demonstrated that SFG reduced CatSper current of human sperm. Structure-based molecular docking analysis suggested that SFG could bind within the ion-conducting pore of CatSper, likely obstructing Ca²⁺ permeation path into sperm cytoplasm. Moreover, SFG exposure impaired human sperm viability, motility and capacitation-associated events, including hyperactivation, protein tyrosine phosphorylation and acrosome reaction. Collectively, out findings propose that SFG disrupts human sperm functions through attenuating CatSper activity, suggesting its potential risks to male fertility.