Balaji Thotakura, Ramanathan Manickam, Menon Venugopal Padmanabhan
Department of Anatomy, Faculty of Medicine, Annamalai University, Annamalainagar, Tamilnadu, India.
Toxicology. 2007 May 5;234(1-2):135-44. doi: 10.1016/j.tox.2007.02.011. Epub 2007 Feb 24.
Accumulating evidence on constitutive expression of cyclooxygenase-2 (COX-2), one of the isoforms of enzyme cyclooxygenase (COX) the other isoform being cyclooxygenase-1 (COX-1), questions the safety profile of non-steroidal anti-inflammatory drugs (NSAIDs). This COX-2 isoform which is induced not only during inflammation but also by factors such as cytokines, steroid hormones and mitogenic stimuli is constitutively expressed in brain, kidney and reproductive organs. Present NSAIDs, particularly COX-2 inhibitors is no longer considered safe since suppression of COX-2 in tissues which it is constitutively expressed may lead to adverse effects. Though intense expression of COX-2 in vas deferens is proved, lack of information with respect to its function has attracted a wide scope for research as to whether COX-2 in vas deferens contributes to male fertility. In the present study, the authors investigated the localization of COX-2 as well as COX-1 in mice vas deferens and also assessed the activity of COX-2 and total prostaglandin (PG) levels in vas deferens. Further they suppressed the expression of COX-2 using a preferential COX-2 inhibitor nimesulide and analyzed the sperm from vas deferens for any defects. COX-2 was intensely expressed in the epithelial cells of mice vas deferens and nimesulide was able to effectively suppress most of COX-2 expression. A decrease in PG levels was observed initially but interestingly, the levels tend to rise on sustained suppression of COX-2. The motility of sperm was affected severely after 6h of nimesulide administration that suggested a crucial role of COX-2 towards fertility of mice sperm.
越来越多的证据表明环氧化酶-2(COX-2)的组成性表达,环氧化酶(COX)有两种同工型,另一种同工型是环氧化酶-1(COX-1),这对非甾体抗炎药(NSAIDs)的安全性提出了质疑。这种COX-2同工型不仅在炎症期间被诱导,还可被细胞因子、类固醇激素和有丝分裂刺激等因素诱导,在脑、肾和生殖器官中组成性表达。目前的非甾体抗炎药,尤其是COX-2抑制剂,不再被认为是安全的,因为在其组成性表达的组织中抑制COX-2可能会导致不良反应。尽管已证实COX-2在输精管中有强烈表达,但关于其功能的信息缺乏,这引发了关于输精管中的COX-2是否对男性生育有贡献的广泛研究。在本研究中,作者研究了COX-2以及COX-1在小鼠输精管中的定位,并评估了输精管中COX-2的活性和总前列腺素(PG)水平。此外,他们使用选择性COX-2抑制剂尼美舒利抑制COX-2的表达,并分析输精管中的精子是否存在任何缺陷。COX-2在小鼠输精管的上皮细胞中强烈表达,尼美舒利能够有效抑制大部分COX-2的表达。最初观察到PG水平下降,但有趣的是,在持续抑制COX-2后,水平趋于上升。给予尼美舒利6小时后,精子活力受到严重影响,这表明COX-2对小鼠精子的生育能力起着关键作用。