Psychostimulant-induced testicular toxicity in mice: Evidence of cocaine and caffeine effects on the local dopaminergic system
Several organ systems can be affected by psychostimulant toxicity. However, there is not sufficient evidence about the impact of psychostimulant intake on testicular physiology and catecholaminergic systems. The aim of the present study was to further explore potential toxic consequences of chronic...
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2015
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v10_n11_p_Gonzalez http://hdl.handle.net/20.500.12110/paper_19326203_v10_n11_p_Gonzalez |
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paper:paper_19326203_v10_n11_p_Gonzalez2023-06-08T16:30:26Z Psychostimulant-induced testicular toxicity in mice: Evidence of cocaine and caffeine effects on the local dopaminergic system adenosine A1 receptor caffeine catalase cocaine copper zinc superoxide dismutase cycline dopamine 1 receptor dopamine 2 receptor follitropin receptor glutathione peroxidase luteinizing hormone receptor messenger RNA protein Bax thiobarbituric acid reactive substance tyrosine 3 monooxygenase adenosine A1 receptor caffeine central stimulant agent cocaine dopamine dopamine 1 receptor dopamine 2 receptor dopamine uptake inhibitor Drd1a protein, mouse DRD2 protein, mouse free radical glutathione peroxidase messenger RNA primer DNA thiobarbituric acid reactive substance tyrosine 3 monooxygenase animal cell animal experiment animal model animal tissue Article cell loss cell proliferation cellular distribution controlled study disease association dopaminergic system down regulation gene expression regulation germ cell intoxication Leydig cell lipid peroxidation long term exposure male male genital tract parameters meiotic germs cell mouse nonhuman protein expression psychostimulant induced testicular toxicity seminiferous tubule volume Sertoli cell spermatogonium testis disease transgenic mouse upregulation animal apoptosis C57BL mouse cytoplasm drug effects genetic epigenesis immunohistochemistry metabolism testis Animals Apoptosis Caffeine Cell Proliferation Central Nervous System Stimulants Cocaine Cytoplasm DNA Primers Dopamine Dopamine Uptake Inhibitors Epigenesis, Genetic Free Radicals Glutathione Peroxidase Immunohistochemistry Leydig Cells Male Mice Mice, Inbred C57BL Receptor, Adenosine A1 Receptors, Dopamine D1 Receptors, Dopamine D2 RNA, Messenger Spermatogonia Testis Thiobarbituric Acid Reactive Substances Tyrosine 3-Monooxygenase Several organ systems can be affected by psychostimulant toxicity. However, there is not sufficient evidence about the impact of psychostimulant intake on testicular physiology and catecholaminergic systems. The aim of the present study was to further explore potential toxic consequences of chronic exposure to cocaine, caffeine, and their combination on testicular physiology. Mice were injected with a 13-day chronic binge regimen of caffeine (3x5mg/kg), cocaine (3×10mg/kg), or combined administration. Mice treated with cocaine alone or combined with caffeine showed reduced volume of the seminiferous tubule associated to a reduction in the number of spermatogonia. Cocaine-only and combined treatments induced increased lipid peroxidation evaluated by TBARS assay and decreased glutathione peroxidase mRNA expression. Importantly, caffeine-cocaine combination potentiated the cocaine-induced germ cell loss, and induced pro-apoptotic BAX protein expression and diminished adenosine receptor A1 mRNA levels. We analyzed markers of dopaminergic function in the testis and detected the presence of tyrosine hydroxylase (TH) in the cytoplasm of androgen-producing Leydig cells, but also in meiotic germs cells within seminiferous tubules. Moreover, using transgenic BAC-Drd1a-tdTomato and D2R-eGFP mice, we report for the first time the presence of dopamine receptors (DRs) D1 and D2 in testicular mouse Leydig cells. Interestingly, the presence of DRD1 was also detected in the spermatogonia nearest the basal lamina of the seminiferous tubules, which did not show TH staining. We observed that psychostimulants induced downregulation of DRs mRNA expression and upregulation of TH protein expression in the testis. These findings suggest a potential role of the local dopaminergic system in psychostimulant-induced testicular pathology. 2015 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v10_n11_p_Gonzalez http://hdl.handle.net/20.500.12110/paper_19326203_v10_n11_p_Gonzalez |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
adenosine A1 receptor caffeine catalase cocaine copper zinc superoxide dismutase cycline dopamine 1 receptor dopamine 2 receptor follitropin receptor glutathione peroxidase luteinizing hormone receptor messenger RNA protein Bax thiobarbituric acid reactive substance tyrosine 3 monooxygenase adenosine A1 receptor caffeine central stimulant agent cocaine dopamine dopamine 1 receptor dopamine 2 receptor dopamine uptake inhibitor Drd1a protein, mouse DRD2 protein, mouse free radical glutathione peroxidase messenger RNA primer DNA thiobarbituric acid reactive substance tyrosine 3 monooxygenase animal cell animal experiment animal model animal tissue Article cell loss cell proliferation cellular distribution controlled study disease association dopaminergic system down regulation gene expression regulation germ cell intoxication Leydig cell lipid peroxidation long term exposure male male genital tract parameters meiotic germs cell mouse nonhuman protein expression psychostimulant induced testicular toxicity seminiferous tubule volume Sertoli cell spermatogonium testis disease transgenic mouse upregulation animal apoptosis C57BL mouse cytoplasm drug effects genetic epigenesis immunohistochemistry metabolism testis Animals Apoptosis Caffeine Cell Proliferation Central Nervous System Stimulants Cocaine Cytoplasm DNA Primers Dopamine Dopamine Uptake Inhibitors Epigenesis, Genetic Free Radicals Glutathione Peroxidase Immunohistochemistry Leydig Cells Male Mice Mice, Inbred C57BL Receptor, Adenosine A1 Receptors, Dopamine D1 Receptors, Dopamine D2 RNA, Messenger Spermatogonia Testis Thiobarbituric Acid Reactive Substances Tyrosine 3-Monooxygenase |
| spellingShingle |
adenosine A1 receptor caffeine catalase cocaine copper zinc superoxide dismutase cycline dopamine 1 receptor dopamine 2 receptor follitropin receptor glutathione peroxidase luteinizing hormone receptor messenger RNA protein Bax thiobarbituric acid reactive substance tyrosine 3 monooxygenase adenosine A1 receptor caffeine central stimulant agent cocaine dopamine dopamine 1 receptor dopamine 2 receptor dopamine uptake inhibitor Drd1a protein, mouse DRD2 protein, mouse free radical glutathione peroxidase messenger RNA primer DNA thiobarbituric acid reactive substance tyrosine 3 monooxygenase animal cell animal experiment animal model animal tissue Article cell loss cell proliferation cellular distribution controlled study disease association dopaminergic system down regulation gene expression regulation germ cell intoxication Leydig cell lipid peroxidation long term exposure male male genital tract parameters meiotic germs cell mouse nonhuman protein expression psychostimulant induced testicular toxicity seminiferous tubule volume Sertoli cell spermatogonium testis disease transgenic mouse upregulation animal apoptosis C57BL mouse cytoplasm drug effects genetic epigenesis immunohistochemistry metabolism testis Animals Apoptosis Caffeine Cell Proliferation Central Nervous System Stimulants Cocaine Cytoplasm DNA Primers Dopamine Dopamine Uptake Inhibitors Epigenesis, Genetic Free Radicals Glutathione Peroxidase Immunohistochemistry Leydig Cells Male Mice Mice, Inbred C57BL Receptor, Adenosine A1 Receptors, Dopamine D1 Receptors, Dopamine D2 RNA, Messenger Spermatogonia Testis Thiobarbituric Acid Reactive Substances Tyrosine 3-Monooxygenase Psychostimulant-induced testicular toxicity in mice: Evidence of cocaine and caffeine effects on the local dopaminergic system |
| topic_facet |
adenosine A1 receptor caffeine catalase cocaine copper zinc superoxide dismutase cycline dopamine 1 receptor dopamine 2 receptor follitropin receptor glutathione peroxidase luteinizing hormone receptor messenger RNA protein Bax thiobarbituric acid reactive substance tyrosine 3 monooxygenase adenosine A1 receptor caffeine central stimulant agent cocaine dopamine dopamine 1 receptor dopamine 2 receptor dopamine uptake inhibitor Drd1a protein, mouse DRD2 protein, mouse free radical glutathione peroxidase messenger RNA primer DNA thiobarbituric acid reactive substance tyrosine 3 monooxygenase animal cell animal experiment animal model animal tissue Article cell loss cell proliferation cellular distribution controlled study disease association dopaminergic system down regulation gene expression regulation germ cell intoxication Leydig cell lipid peroxidation long term exposure male male genital tract parameters meiotic germs cell mouse nonhuman protein expression psychostimulant induced testicular toxicity seminiferous tubule volume Sertoli cell spermatogonium testis disease transgenic mouse upregulation animal apoptosis C57BL mouse cytoplasm drug effects genetic epigenesis immunohistochemistry metabolism testis Animals Apoptosis Caffeine Cell Proliferation Central Nervous System Stimulants Cocaine Cytoplasm DNA Primers Dopamine Dopamine Uptake Inhibitors Epigenesis, Genetic Free Radicals Glutathione Peroxidase Immunohistochemistry Leydig Cells Male Mice Mice, Inbred C57BL Receptor, Adenosine A1 Receptors, Dopamine D1 Receptors, Dopamine D2 RNA, Messenger Spermatogonia Testis Thiobarbituric Acid Reactive Substances Tyrosine 3-Monooxygenase |
| description |
Several organ systems can be affected by psychostimulant toxicity. However, there is not sufficient evidence about the impact of psychostimulant intake on testicular physiology and catecholaminergic systems. The aim of the present study was to further explore potential toxic consequences of chronic exposure to cocaine, caffeine, and their combination on testicular physiology. Mice were injected with a 13-day chronic binge regimen of caffeine (3x5mg/kg), cocaine (3×10mg/kg), or combined administration. Mice treated with cocaine alone or combined with caffeine showed reduced volume of the seminiferous tubule associated to a reduction in the number of spermatogonia. Cocaine-only and combined treatments induced increased lipid peroxidation evaluated by TBARS assay and decreased glutathione peroxidase mRNA expression. Importantly, caffeine-cocaine combination potentiated the cocaine-induced germ cell loss, and induced pro-apoptotic BAX protein expression and diminished adenosine receptor A1 mRNA levels. We analyzed markers of dopaminergic function in the testis and detected the presence of tyrosine hydroxylase (TH) in the cytoplasm of androgen-producing Leydig cells, but also in meiotic germs cells within seminiferous tubules. Moreover, using transgenic BAC-Drd1a-tdTomato and D2R-eGFP mice, we report for the first time the presence of dopamine receptors (DRs) D1 and D2 in testicular mouse Leydig cells. Interestingly, the presence of DRD1 was also detected in the spermatogonia nearest the basal lamina of the seminiferous tubules, which did not show TH staining. We observed that psychostimulants induced downregulation of DRs mRNA expression and upregulation of TH protein expression in the testis. These findings suggest a potential role of the local dopaminergic system in psychostimulant-induced testicular pathology. |
| title |
Psychostimulant-induced testicular toxicity in mice: Evidence of cocaine and caffeine effects on the local dopaminergic system |
| title_short |
Psychostimulant-induced testicular toxicity in mice: Evidence of cocaine and caffeine effects on the local dopaminergic system |
| title_full |
Psychostimulant-induced testicular toxicity in mice: Evidence of cocaine and caffeine effects on the local dopaminergic system |
| title_fullStr |
Psychostimulant-induced testicular toxicity in mice: Evidence of cocaine and caffeine effects on the local dopaminergic system |
| title_full_unstemmed |
Psychostimulant-induced testicular toxicity in mice: Evidence of cocaine and caffeine effects on the local dopaminergic system |
| title_sort |
psychostimulant-induced testicular toxicity in mice: evidence of cocaine and caffeine effects on the local dopaminergic system |
| publishDate |
2015 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v10_n11_p_Gonzalez http://hdl.handle.net/20.500.12110/paper_19326203_v10_n11_p_Gonzalez |
| _version_ |
1768541772025167872 |