Phosphodiesterase 10A inhibitor PF-2545920 as a prospective agent for the clinical promotion of sperm motility  

作　　者：Yi-Ting Yang Bin Yan Yu-Hua Li Li-Na Guo Wei-Wei Wang Li-Jie Liu He-Guo Yu Hua Diao 

机构地区：[1]NHC Key Laboratory of Reproduction Regulation(Shanghai Institute for Biomedical and Pharmaceutical Technologies),School of Basic Medical Sciences,Fudan University,Shanghai 200032,China [2]Reproductive Medicine Centre,Zhongshan Hospital,Fudan University,Shanghai 200032,China [3]School of Basic Medical Sciences,Fudan University,Shanghai 200032,China [4]Department of Urology,Huashan Hospital,Fudan University,Shanghai 200040,China

出　　处：《Asian Journal of Andrology》2023年第5期608-615,共8页亚洲男性学杂志（英文版）

基　　金：supported by the Shanghai Municipal Health Commission Young Foundation(No.20194Y0270);Science and Technology Commission of Shanghai Municipality(No.20ZR1448100).

摘　　要：Phosphodiesterase(PDE)inhibitors can improve sperm motility in patients with asthenozoospermia.However,the most commonly reported nonselective PDE inhibitor pentoxifylline and PDE5 inhibitor sildenafil have the disadvantages of requiring a high concentration and destroying sperm integrity.We examined the PDE10A inhibitor PF-2545920 to compare its ability to promote sperm motility with that of pentoxifylline and sildenafil.After seminal plasma was discarded,several semen samples were subjected to four treatments(control,PF-2545920,pentoxifylline,and sildenafil)to evaluate their ability to affect motility,viability,and spontaneous acrosome reactions.Intracellular calcium and adenosine triphosphate(ATP),mitochondrial membrane potential,and penetration through viscous medium were assessed by flow cytometry,luciferase,and hyaluronic acid after treatment with PF-2545920.Statistical analyses were performed using the analysis of variance statistical test.PF-2545920 elevated the percentage of motile spermatozoa compared to the control,pentoxifylline,and sildenafil groups at 10μmol l^(-1)(P<0.01).It is less toxic to GC-2spd mouse spermatocytes cells and spermatozoa and causes fewer spontaneous acrosomal reactions(P<0.05).PF-2545920 also increased mitochondrial membrane potential(P<0.001)and altered intracellular calcium(P<0.05)in a dose-dependent manner,including increasing sperm hyaluronic acid penetrating ability(P<0.05).Therefore,PF-2545920 might be an excellent choiceforstimulatingthe spermmotility.

关 键 词：PENTOXIFYLLINE phosphodiesterase 10A SILDENAFIL sperm motility spontaneous acrosome reaction 

分 类 号：R73[医药卫生—肿瘤]