Siva Archana B, Yeung Ching-Hei, Cooper Trevor G, Shivaji Sisinthy
Centre for Cellular and Molecular Biology (CCMB), Uppal Road, Hyderabad, India.
Reprod Toxicol. 2006 Nov;22(4):702-9. doi: 10.1016/j.reprotox.2006.04.013. Epub 2006 Jun 14.
To be fertilization competent, spermatozoa undergo a series of changes in the female reproductive tract collectively referred to as capacitation. In an attempt to understand, if ornidazole, a known anti-fertility drug, adversely affects sperm functions by targeting capacitation, we designed experiments to study the influence of this drug on hyperactivation (HA), capacitation-associated protein tyrosine phosphorylation (pY) and the acrosome reaction (AR). Addition of ornidazole at 0 h, inhibited the onset of HA and total pY in a dose dependent manner. However, when ornidazole was added at 3.5h, severe effects were still seen on HA and pY of high molecular weight proteins but, pY of lower M(r) proteins (50-56 kDa) was affected only marginally. Further, lower doses of ornidazole (5 and 10 mM) had greater inhibitory effect when added at 0 h, while addition of ornidazole at 3.5 h required higher doses of ornidazole (25 mM) to cause significant inhibition of acrosome reaction. Collectively, through in vitro studies, we demonstrate that ornidazole affects the onset and progression of hamster sperm hyperactivation, capacitation associated protein tyrosine phosphorylation and acrosome reaction, and the severity depends on the dose (5, 10 or 25 mM) and the time of addition (0 or 3.5 h) of the drug to the spermatozoa.
为具备受精能力,精子在雌性生殖道中会经历一系列变化,这些变化统称为获能。为了了解已知的抗生育药物奥硝唑是否通过靶向获能对精子功能产生不利影响,我们设计了实验来研究该药物对超活化(HA)、获能相关蛋白酪氨酸磷酸化(pY)和顶体反应(AR)的影响。在0小时添加奥硝唑以剂量依赖的方式抑制了HA的起始和总pY。然而,当在3.5小时添加奥硝唑时,对高分子量蛋白的HA和pY仍有严重影响,但较低分子量(50 - 56 kDa)蛋白的pY仅受到轻微影响。此外,较低剂量的奥硝唑(5和10 mM)在0小时添加时具有更大的抑制作用,而在3.5小时添加奥硝唑则需要更高剂量(25 mM)才能显著抑制顶体反应。总体而言,通过体外研究,我们证明奥硝唑会影响仓鼠精子超活化、获能相关蛋白酪氨酸磷酸化和顶体反应的起始和进程,其严重程度取决于药物添加到精子中的剂量(5、10或25 mM)和时间(0或3.5小时)。