Bezafibrate alleviates diabetes-induced spermatogenesis dysfunction by inhibiting inflammation and oxidative stress
The metabolic disorders caused by diabetes can lead to various complications, including male spermatogenesis dysfunction. Exploring effective therapeutics that attenuate diabetes mellitus (DM)-induced male subfertility is of great importance. Pharmaceuticals targeting PPARα activation such as bezafi...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024043159 |
| _version_ | 1797224142045446144 |
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| author | Yang Mu Ling-Bo Luo Shu-juan Wu Yue Gao Xiao-lin Qin Jing Zhao Qian Liu Jing Yang |
| author_facet | Yang Mu Ling-Bo Luo Shu-juan Wu Yue Gao Xiao-lin Qin Jing Zhao Qian Liu Jing Yang |
| author_sort | Yang Mu |
| collection | DOAJ |
| description | The metabolic disorders caused by diabetes can lead to various complications, including male spermatogenesis dysfunction. Exploring effective therapeutics that attenuate diabetes mellitus (DM)-induced male subfertility is of great importance. Pharmaceuticals targeting PPARα activation such as bezafibrate have been regarded as an important strategy for patients with diabetes. In this study, we use streptozocin (STZ) injection to establish a type 1 DM mice model and use bezafibrate to treat DM mice and evaluate the effects of bezafibrate on the spermatogenic function of the DM male mice. Bezafibrate treatment exhibited protective effects on DM-induced spermatogenesis deficiency, as reflected by increased testis weight, improved histological morphology of testis, elevated sperm parameters, increased serum testosterone concentration as well as increased mRNA levels of steroidogenesis enzymes. Meanwhile, testicular cell apoptosis, inflammation accumulation and oxidative stress status were also shown to be alleviated by bezafibrate compared with the DM group. In vivo and in vitro studies, PPARα specific inhibitor and PPARα knockout mice were further used to investigate the role of PPARα in the protective effects of bezafibrate on DM-induced spermatogenesis dysfunction. Our results indicated that the protection of bezafibrate on DM-induced spermatogenesis deficiency was abrogated by PPARα inhibition or deletion. Our study suggested that bezafibrate administration could ameliorate DM-induced spermatogenesis dysfunction and may represent a novel practical strategy for male infertility. |
| first_indexed | 2024-04-24T13:48:25Z |
| format | Article |
| id | doaj.art-9607bee035b8401aba6161e3d08c5a95 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-24T13:48:25Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-9607bee035b8401aba6161e3d08c5a952024-04-04T05:07:07ZengElsevierHeliyon2405-84402024-03-01106e28284Bezafibrate alleviates diabetes-induced spermatogenesis dysfunction by inhibiting inflammation and oxidative stressYang Mu0Ling-Bo Luo1Shu-juan Wu2Yue Gao3Xiao-lin Qin4Jing Zhao5Qian Liu6Jing Yang7Reproductive Medicine Center, Renmin Hospital of Wuhan University, Wuhan, 430060, ChinaReproductive Medicine Center, Renmin Hospital of Wuhan University, Wuhan, 430060, ChinaReproductive Medicine Center, Renmin Hospital of Wuhan University, Wuhan, 430060, ChinaReproductive Medicine Center, Renmin Hospital of Wuhan University, Wuhan, 430060, ChinaReproductive Medicine Center, Renmin Hospital of Wuhan University, Wuhan, 430060, ChinaReproductive Medicine Center, Renmin Hospital of Wuhan University, Wuhan, 430060, China; Corresponding author.Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, 430060, China; Corresponding author.Reproductive Medicine Center, Renmin Hospital of Wuhan University, Wuhan, 430060, China; Corresponding author.The metabolic disorders caused by diabetes can lead to various complications, including male spermatogenesis dysfunction. Exploring effective therapeutics that attenuate diabetes mellitus (DM)-induced male subfertility is of great importance. Pharmaceuticals targeting PPARα activation such as bezafibrate have been regarded as an important strategy for patients with diabetes. In this study, we use streptozocin (STZ) injection to establish a type 1 DM mice model and use bezafibrate to treat DM mice and evaluate the effects of bezafibrate on the spermatogenic function of the DM male mice. Bezafibrate treatment exhibited protective effects on DM-induced spermatogenesis deficiency, as reflected by increased testis weight, improved histological morphology of testis, elevated sperm parameters, increased serum testosterone concentration as well as increased mRNA levels of steroidogenesis enzymes. Meanwhile, testicular cell apoptosis, inflammation accumulation and oxidative stress status were also shown to be alleviated by bezafibrate compared with the DM group. In vivo and in vitro studies, PPARα specific inhibitor and PPARα knockout mice were further used to investigate the role of PPARα in the protective effects of bezafibrate on DM-induced spermatogenesis dysfunction. Our results indicated that the protection of bezafibrate on DM-induced spermatogenesis deficiency was abrogated by PPARα inhibition or deletion. Our study suggested that bezafibrate administration could ameliorate DM-induced spermatogenesis dysfunction and may represent a novel practical strategy for male infertility.http://www.sciencedirect.com/science/article/pii/S2405844024043159BezafibrateDiabetes mellitus (DM)Spermatogenesis dysfunctionPPARαInflammationOxidative stress |
| spellingShingle | Yang Mu Ling-Bo Luo Shu-juan Wu Yue Gao Xiao-lin Qin Jing Zhao Qian Liu Jing Yang Bezafibrate alleviates diabetes-induced spermatogenesis dysfunction by inhibiting inflammation and oxidative stress Heliyon Bezafibrate Diabetes mellitus (DM) Spermatogenesis dysfunction PPARα Inflammation Oxidative stress |
| title | Bezafibrate alleviates diabetes-induced spermatogenesis dysfunction by inhibiting inflammation and oxidative stress |
| title_full | Bezafibrate alleviates diabetes-induced spermatogenesis dysfunction by inhibiting inflammation and oxidative stress |
| title_fullStr | Bezafibrate alleviates diabetes-induced spermatogenesis dysfunction by inhibiting inflammation and oxidative stress |
| title_full_unstemmed | Bezafibrate alleviates diabetes-induced spermatogenesis dysfunction by inhibiting inflammation and oxidative stress |
| title_short | Bezafibrate alleviates diabetes-induced spermatogenesis dysfunction by inhibiting inflammation and oxidative stress |
| title_sort | bezafibrate alleviates diabetes induced spermatogenesis dysfunction by inhibiting inflammation and oxidative stress |
| topic | Bezafibrate Diabetes mellitus (DM) Spermatogenesis dysfunction PPARα Inflammation Oxidative stress |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024043159 |
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