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Nicotinamide mononucleotide improves spermatogenic function in streptozotocin-induced diabetic mice via modulating the glycolysis pathway

查看全文 作  者:Duo [1,2]Ma;Linlin [3]Hu;Jinyuan [1,2]Wang;Min [1,2]Luo;Aihong [2]Liang;Xiaocan [1,2]Lei;Biyun [3]Liao;Meixiang [1,2]Li;Ming [2]Xie;Haicheng [2]Li;Yiwei [2]Gong;Dan [2]Zi;Xiangrun [1]Li;Xi [1,2]Chen;Xucai [1]Liao 高影响力作者 机构地区:[1]Hunan Province Collaborative Innovation Base of Endocrinology&Metabolism Science and Education for Postgraduates,The First Affiliated Hospital of Shaoyang University and Hengyang Medical School,University of South China,Hengyang 422000,China;[2]Institute of Clinical Anatomy&Reproductive Medicine,Hengyang Medical School,University of South China,Hengyang 421001,China;[3]Reproductive Medicine Center,The Affiliated Hospital of Youjiang Medical University for Nationalities,Baise 533000,China高影响力机构 出  处:《Acta Biochimica et Biophysica Sinica》索引2022年第54卷第9期,共11页高影响力期刊 基  金:the grants from the Horizontal Scientific Research Project of The First Affiliated Hospital of Shaoyang University(No.2020HX01);GuangxiNatural ScienceFoundation,China(No.2021GXNSFBA220010);the National Natural Science Foundation of China(No.82101720);the Scientific Research Elevation Project of Young Faculty fromGuangxiUniversities(No.2019KY0567);the Scientific Research and Technological Development Foundation of Baise(No.20183331);the First Batch of Highlevel Talent Scientific Research Projects of the Affiliated Hospital of Youjiang Medical University for Nationalities in 2019(No.R20196317);the National College Students Innovation and Entrepreneurship Training Program(No.X202110555520). 摘  要:Spermatogenic dysfunction is one of the major secondary complications of diabetes;however,the underlying mechanisms remain ill-defined,and there is no available drug or strategy for the radical treatment of diabetic spermatogenic dysfunction.Therefore,the objective of this study is to investigate the protective effects of nicotinamide mononucleotide(NMN)on testicular spermatogenic function in streptozotocin(STZ)-induced diabetic mice.The results show that oral administration of NMN significantly increases the body and testis weight and the number of sperms.Moreover,the abnormal sperm count and the rate of sperm malformation are significantly decreased compared with the saline-treated diabetic mice.Histological analysis reveals that NMN treatment significantly increases the area and diameter of seminiferous tubules,accompanied by an increased number of spermatogenic cells and sperms.Immunohistochemistry and qRT-PCR results show that NMN increases Bcl-2 expression and decreases Bax expression in the testis.NMN also increases the protein expression of Vimentin and the mRNA expressions of WT1 and GATA4.In addition,qRT-PCR,western blot analysis and immunohistochemistry results also show that NMN increases the expressions of glycolysis-related rate-limiting enzymes including HK2,PKM2,and LDHA.In summary,this study demonstrates the protective effects of NMN on the testis in an STZ-induced diabetic mice model.NMN exerts its protective effects via reducing spermatogenic cell apoptosis by regulating glycolysis of Sertoli cells in diabetic mice.This study provides an experimental basis for the future clinical application of NMN in diabetes-induced spermatogenicdysfunction. 关 键 词:nicotinamide mononucleotide DIABETES spermatogenic function Sertoli cell GLYCOLYSIS
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