Localization of cyclooxygenase-2 in mice vas deferens and its effects on fertility upon suppression using nimesulide—A preferential cyclooxygenase-2 inhibitor

Balaji, Thotakura; Ramanathan, Manickam; Menon, Venugopal P.

doi:10.1016/j.tox.2007.02.011

Cited by 12 publications

(10 citation statements)

References 59 publications

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“…With respect to male reproductive organs, COX-2 is detected in the principal epithelial cells of Vas deferens mainly concentrated in the infra-nuclear compartment of the cell. The same pattern of distribution was also observed for COX-1 [12]. Existing reports also state that removal of sperm from lumen of Vas deferens did not alter COX-2 levels.…”

Section: Body Weight and Organ Weightsupporting

confidence: 75%

“…Our previous studies on fatty acid composition of vas deferens shows a steady rise in AA levels following nimesulide administration. Eicosapentaenoic Acid (EPA) and Docosahexanoic Acid (DHA) which was considered to be protective was found to decrease following nimesulide administration [12]. Suppression of COX-2 with subsequent accumulation of AA leading to apoptosis might be PG mediated.…”

Section: Body Weight and Organ Weightmentioning

confidence: 99%

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Nimesulide Induced Histopathological Changes in the Vas Deferens of Mice

Balaji

Subramanian²,

Gnanasundaram³

et al. 2013

JCDR

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Aim: Nimesulide, a preferential COX-2 inhibitor has 20 times more selectivity towards COX-2 than that of COX-1. COX-2 selective inhibitors cause frequent nephrotoxicity and hepatotoxicity following their usage. This proposes a physiological role of COX-2 in kidney and liver. Not much attention has been focused on the role of COX-2 with respect to reproduction especially in male reproduction, and the available information is scanty. Aims and Objectives:The present study aims to investigate the adverse effects of nimesulide in the vas deferens thereby indirectly assess the role of COX-2 in male reproductive tract. Material and Methods:Nimesulide was administered orally and the animals were maintained for different time periods prior to sacrifice. Results:The vas deferens of nimesulide treated mice showed extensive histopathological changes such as vacoulation and exfoliation of cells in the epithelial layer. Conclusion:Nimesulide administration leads to cytotoxic effects suggestive of apoptosis in the vas deferens of mice.

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Section: Body Weight and Organ Weightsupporting

confidence: 75%

Section: Body Weight and Organ Weightmentioning

confidence: 99%

Nimesulide Induced Histopathological Changes in the Vas Deferens of Mice

Balaji

Subramanian²,

Gnanasundaram³

et al. 2013

JCDR

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“…Very-long-chain ity ( 8 ). In addition to the presence of HUFAs in mammalian testis and spermatozoa, there are also very-long-chain polyunsaturated fatty acids (VLPUFAs) that contain C26-C38 hydrocarbon chains (9)(10)(11).…”

Section: Fatty Acid Extraction and Gc-ms Analysismentioning

confidence: 99%

“…In monkey sperm, 99% of DHA is present in fl agella ( 6 ). Thus, the failure of spermatogenesis at a late stage of spermiogenesis may be at least in restore male reproduction and spermiogenesis because of proposed roles of AA as eicosanoid precursor in male reproductive function ( 7,8 ). Although the underlying mechanism is yet to be elucidated, there could be a functional redundancy that might compensate for the lack of eicosanoids.…”

Section: Testis Dha and Cholesta-35-diene Were Restored By Dietary Dhamentioning

confidence: 99%

Docosahexaenoic acid supplementation fully restores fertility and spermatogenesis in male delta-6 desaturase-null mice

Roqueta‐Rivera

Stroud

Haschek

et al. 2010

Journal of Lipid Research

132

118

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This article is available online at http://www.jlr.org Supplementary key words essential fatty acids • arachidonic acid • highly unsaturated fatty acids • very-long-chain polyunsaturated fatty acids • choelsta-3,5-diene • male reproduction • spermiogenesis Delta-6 desaturase (D6D) is the fi rst and rate-limiting enzyme for highly unsaturated fatty acid (HUFA) synthesis that consists of a series of elongation and desaturation reactions ( 1 ). The dietary essential fatty acids 18:2n-6 (linoleic acid) and 18:3n-3 ( ␣ -linolenic acid) are substrates for D6D and precursors of physiologically important HUFAs, such as 20:4n-6 [arachidonic acid (AA)], 22:5n6 [docosapentaenoic acid (DPAn6)], and 22:6n3 [docosahexaenoic acid (DHA)]. D6D is also required for the fi nal desaturation step for the synthesis of DPAn6 and DHA.These HUFAs are present in high concentration in testes and sperm of mammals. DPAn6, a HUFA derived from AA, dramatically increases in rat testes during the sexual maturation stage ( 2 ). In mice, AA, DPAn6, and DHA are abundant in membrane phospholipids of round spermatids ( 3 ) and mature mouse spermatozoa ( 4 ), suggesting an important role for these fatty acids for proper spermatogenesis. In humans, DHA is the main HUFA in sperm ( 5 ). DHA is specifi cally high in the sperm tail when compared with the sperm head in monkeys ( 6 ), implying a role of DHA in sperm tail function. AA may also have a role in male fertility as a precursor to eicosanoids. Prostaglandin E2, for example, has been shown to increase sperm motility ( 7 ), while inhibition of cycloxygenase-2 in mouse vas deferens results in a decrease of sperm motility and fertilAbstract Delta-6 desaturase-null mice ( ؊ / ؊ ) are unable to synthesize highly unsaturated fatty acids (HUFAs): arachidonic acid (AA), docosahexaenoic acid (DHA), and n6-docosapentaenoic acid (DPAn6). The ؊ / ؊ males exhibit infertility and arrest of spermatogenesis at late spermiogenesis. To determine which HUFA is essential for spermiogenesis, a diet supplemented with either 0.2% (w/w) AA or DHA was fed to wild-type ( Abbreviations: AA, arachidonic acid; CD, cholesta-3,5-diene; D6D, ⌬ 6 desaturase; DHA, docosahexaenoic acid; DPAn6, docosapentaenoic acid; FAME, fatty acid methyl esters; HUFA, highly unsaturated fatty acid; VLPUFA, very-long-chain polyunsaturated fatty acid.

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“…Earlier study has revealed that COX-2 is the dominant isoform species in the seminal vesicle and COX-1 is the dominant isoform species in the testes of humans and monkeys (14) . Recent studies have indicated constitutive expression of COX-2 in the brain, kidney, uterus, ovary, and vas deferens (15) . COX-1 and COX-2 inhibitors interfere with arachidonic acid metabolism, and accumulation of arachidonic acid in infl amed cells is cytotoxic and induces apoptosis (16,17) .…”

Section: Discussionmentioning

confidence: 99%