du Plessis S S, Franken D R, Baldi E, Luconi M
Department of Medical Physiology and Biochemistry, Faculty of Health Sciences, University of Stellenbosch, PO Box 19063, Tygerberg 7505, South Africa.
Int J Androl. 2004 Feb;27(1):19-26. doi: 10.1111/j.1365-2605.2004.00440.x.
Various signalling pathways are involved in the regulation of sperm motility, capacitation, acrosome reaction and sperm-zona binding. Recent data pointed out an important role for phosphatidylinositol 3-kinase (PI3K) in human sperm motility. However, no study as of yet has been carried out to determine the effect of sperm treatment with the PI3K inhibitor LY294002 on other sperm parameters. In the present study, we investigated the role of PI3K on human sperm motility, acrosome reaction and sperm-oocyte binding by using this inhibitor. We demonstrate that in vitro incubation of washed unselected spermatozoa with LY294002 increased the percentage motility and progressive motility in asthenozoospermia patients as evaluated by computer-aided sperm analysis. The compound furthermore did not influence the acrosome reaction, whilst it (further) slightly enhanced sperm-oocyte binding. Our results therefore imply that PI3K negatively affects sperm motility and oocyte binding and might suggest a possible therapeutic role for PI3K inhibitors in the treatment regime for asthenozoospermia.
多种信号通路参与精子运动、获能、顶体反应及精子与透明带结合的调控。近期数据指出磷脂酰肌醇3激酶(PI3K)在人类精子运动中起重要作用。然而,截至目前尚未开展研究来确定用PI3K抑制剂LY294002处理精子对其他精子参数的影响。在本研究中,我们通过使用该抑制剂研究了PI3K在人类精子运动、顶体反应及精子-卵母细胞结合中的作用。我们证明,通过计算机辅助精子分析评估,用LY294002体外孵育未经筛选的洗涤精子可提高弱精子症患者的精子活力百分比和前向运动能力。该化合物此外不影响顶体反应,同时它(进一步)轻微增强精子-卵母细胞结合。因此,我们的结果表明PI3K对精子运动和卵母细胞结合有负面影响,并可能提示PI3K抑制剂在弱精子症治疗方案中可能具有治疗作用。