Mariem B. Rhouma, Massimo Venditti, Asma Haddadi, Latifa Knani, Lina Chouchene, Sana Boughammoura, Russel J. Reiter, Sergio Minucci, Imed Messaoudi
{"title":"褪黑激素通过雷帕霉素机制靶标(mTOR)途径抵消镉诱导的大鼠睾丸毒性。","authors":"Mariem B. Rhouma, Massimo Venditti, Asma Haddadi, Latifa Knani, Lina Chouchene, Sana Boughammoura, Russel J. Reiter, Sergio Minucci, Imed Messaoudi","doi":"10.1002/jez.2792","DOIUrl":null,"url":null,"abstract":"<p>The protective action of melatonin (MLT) against the harmful effects of cadmium (Cd) on testicular activity in rats has been documented previously; however, the involved molecular mechanisms have yet to be elucidated. Herein, we investigate the involvement of the mammalian target of rapamycin (mTOR) on the ability of MLT to counteract the damage induced by Cd on the rat testicular activity. Our study confirmed that Cd has harmful effects on the testes of rats and the protective action exerted by MLT. We reported, for the first time, that the addition of rapamycin (Rapa), a specific mTOR inhibitor, to animals co-treated with Cd and MLT completely abolished the beneficial effects exerted by MLT, indicating that the mTOR pathway partially modulates its helpful effects on Cd testicular toxicity. Interestingly, Rapa-alone treatment, provoking mTOR inhibition, produced altered morphological parameters, increased autophagy of germ and somatic cells, and reduced serum testosterone concentration. In addition, mTOR inhibition also reduced protein levels of markers of steroidogenesis (3β-Hydroxysteroid dehydrogenase) and blood–testis barrier integrity (occludin and connexin 43). Finally, Rapa altered sperm parameters as well as the ability of mature spermatozoa to perform a proper acrosome reaction. Although further investigation is needed to better clarify the molecular pathway involved in MLT action, we confirm that MLT alleviating Cd effects can be used as a supplement to enhance testicular function and improve male gamete quality.</p>","PeriodicalId":15711,"journal":{"name":"Journal of experimental zoology. Part A, Ecological and integrative physiology","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Melatonin counteracts cadmium-induced rat testicular toxicity via the mechanistic target rapamycin (mTOR) pathway\",\"authors\":\"Mariem B. Rhouma, Massimo Venditti, Asma Haddadi, Latifa Knani, Lina Chouchene, Sana Boughammoura, Russel J. Reiter, Sergio Minucci, Imed Messaoudi\",\"doi\":\"10.1002/jez.2792\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>The protective action of melatonin (MLT) against the harmful effects of cadmium (Cd) on testicular activity in rats has been documented previously; however, the involved molecular mechanisms have yet to be elucidated. Herein, we investigate the involvement of the mammalian target of rapamycin (mTOR) on the ability of MLT to counteract the damage induced by Cd on the rat testicular activity. Our study confirmed that Cd has harmful effects on the testes of rats and the protective action exerted by MLT. We reported, for the first time, that the addition of rapamycin (Rapa), a specific mTOR inhibitor, to animals co-treated with Cd and MLT completely abolished the beneficial effects exerted by MLT, indicating that the mTOR pathway partially modulates its helpful effects on Cd testicular toxicity. Interestingly, Rapa-alone treatment, provoking mTOR inhibition, produced altered morphological parameters, increased autophagy of germ and somatic cells, and reduced serum testosterone concentration. In addition, mTOR inhibition also reduced protein levels of markers of steroidogenesis (3β-Hydroxysteroid dehydrogenase) and blood–testis barrier integrity (occludin and connexin 43). Finally, Rapa altered sperm parameters as well as the ability of mature spermatozoa to perform a proper acrosome reaction. Although further investigation is needed to better clarify the molecular pathway involved in MLT action, we confirm that MLT alleviating Cd effects can be used as a supplement to enhance testicular function and improve male gamete quality.</p>\",\"PeriodicalId\":15711,\"journal\":{\"name\":\"Journal of experimental zoology. 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Melatonin counteracts cadmium-induced rat testicular toxicity via the mechanistic target rapamycin (mTOR) pathway
The protective action of melatonin (MLT) against the harmful effects of cadmium (Cd) on testicular activity in rats has been documented previously; however, the involved molecular mechanisms have yet to be elucidated. Herein, we investigate the involvement of the mammalian target of rapamycin (mTOR) on the ability of MLT to counteract the damage induced by Cd on the rat testicular activity. Our study confirmed that Cd has harmful effects on the testes of rats and the protective action exerted by MLT. We reported, for the first time, that the addition of rapamycin (Rapa), a specific mTOR inhibitor, to animals co-treated with Cd and MLT completely abolished the beneficial effects exerted by MLT, indicating that the mTOR pathway partially modulates its helpful effects on Cd testicular toxicity. Interestingly, Rapa-alone treatment, provoking mTOR inhibition, produced altered morphological parameters, increased autophagy of germ and somatic cells, and reduced serum testosterone concentration. In addition, mTOR inhibition also reduced protein levels of markers of steroidogenesis (3β-Hydroxysteroid dehydrogenase) and blood–testis barrier integrity (occludin and connexin 43). Finally, Rapa altered sperm parameters as well as the ability of mature spermatozoa to perform a proper acrosome reaction. Although further investigation is needed to better clarify the molecular pathway involved in MLT action, we confirm that MLT alleviating Cd effects can be used as a supplement to enhance testicular function and improve male gamete quality.
期刊介绍:
The Journal of Experimental Zoology – A publishes articles at the interface between Development, Physiology, Ecology and Evolution. Contributions that help to reveal how molecular, functional and ecological variation relate to one another are particularly welcome. The Journal publishes original research in the form of rapid communications or regular research articles, as well as perspectives and reviews on topics pertaining to the scope of the Journal. Acceptable articles are limited to studies on animals.