Journal
TOXICOLOGY
Volume 234, Issue 1-2, Pages 135-144Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2007.02.011
Keywords
cyclooxygensase-2; fertility; mice; nimesulide; prostaglandins; vas deferens
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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 6 h of nimesulide administration that suggested a crucial role of COX-2 towards fertility of mice sperm. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
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