摘要
目的探究抗肿瘤药物POMHEX对成熟小鼠精子功能的影响。方法将小鼠精子在体外暴露于POMHEX(0.1~100μmol/L),通过计算机辅助精液分析系统评估精子活动率和前向运动精子百分率;伊红-苯胺黑染色法检测精子存活率;荧光素-荧光素酶系统检测精子ATP水平;蛋白质印迹实验检测精子获能相关蛋白质酪氨酸磷酸化;考马斯亮蓝G250染色检测精子顶体反应。结果在不影响存活率的条件下,0.1μmol/L及以上浓度POMHEX可降低小鼠精子活动率(P<0.01)和前向运动精子百分率(P<0.05);1μmol/L及以上浓度可抑制小鼠精子ATP水平(P<0.01)和获能过程蛋白质酪氨酸磷酸化的增加。POMHEX虽然不影响小鼠精子的自发顶体反应,但在5μmol/L及以上浓度会抑制由钙离子载体A23187诱导的顶体反应(P<0.01)。结论抗肿瘤药物POMHEX在体外可抑制小鼠精子运动和获能,对小鼠精子造成生殖毒性。提示接受POMHEX治疗的患者可提前进行生育力保存。
Objective To investigate the effect of anti-cancer drug POMHEX on sperm function in mature mice.Methods Mouse epididymal sperm were exposed to POMHEX(O.1-100μmol/L)in vitro.Total and progressive motility of sperms were assessed using computer-assisted semen analysis system(CASA),and their viability was evaluated by Eosinnigrosine staining.ATP level of sperm was detected by luciferin-luciferase system.Western blot analysis was performed to assess protein phosphorylation,and Coomassie brilliant blue G250 staining was used to estimate acrosome integrity.Results POMHEX with concentrations of≥0.1μmol/L significantly attenuated total and progressive motility of sperms(P<0.05),exhibiting a dose-dependent effect,but no effect on sperm viability.Additionally,POMHEX with concentrations of≥1μmol/L significantly inhibited ATP level in sperms and protein tyrosine phosphorylation during sperm capacitation in mice(P<O.O1).Although there was no effect on the spontaneous acrosome reaction of mouse sperm,POMHEX with concentrations of≥5μmol/L inhibited Ca2*ionophore A23187-induced acrosome reaction(P<0.01).Conclusion Our results reveal that the POMHEX can impede sperm motility and capacitation in vitro,and then potentially result in reproductive toxicity in mouse sperm.Our findings suggest that patients undergoing POMHEX treatment should consider fertility preservation options in advance.
作者
王晓琛
钱高青
樊卫民
刘强
Wang Xiaochen;Qian Gaoqing;Fan Weimin;Liu Qiang(Department of Histoembryology,Genetics and Developmental Biology,Basic Medical College,Shanghai Key Laboratory of Reproductive Medicine,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;State Key Laboratory of Reproductive Medicine and Ofspring Health Nanjing Medical University,Nanjing 211166,Jiangsu,China;Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China)
出处
《中国男科学杂志》
CAS
CSCD
2023年第5期9-14,共6页
Chinese Journal of Andrology
基金
国家自然科学基金(81571488,81771637)。
