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

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 investiga...

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Main Authors: Ma Duo, Hu Linlin, Wang Jinyuan, Luo Min, Liang Aihong, Lei Xiaocan, Liao Biyun, Li Meixiang, Xie Ming, Li Haicheng, Gong Yiwei, Zi Dan, Li Xiangrun, Chen Xi, Liao Xucai
Format: Article
Language:English
Published: China Science Publishing & Media Ltd. 2022-08-01
Series:Acta Biochimica et Biophysica Sinica
Subjects:
Online Access:https://www.sciengine.com/doi/10.3724/abbs.2022099
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author Ma Duo
Hu Linlin
Wang Jinyuan
Luo Min
Liang Aihong
Lei Xiaocan
Liao Biyun
Li Meixiang
Xie Ming
Li Haicheng
Gong Yiwei
Zi Dan
Li Xiangrun
Chen Xi
Liao Xucai
author_facet Ma Duo
Hu Linlin
Wang Jinyuan
Luo Min
Liang Aihong
Lei Xiaocan
Liao Biyun
Li Meixiang
Xie Ming
Li Haicheng
Gong Yiwei
Zi Dan
Li Xiangrun
Chen Xi
Liao Xucai
author_sort Ma Duo
collection DOAJ
description 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 spermatogenic dysfunction.
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spelling doaj.art-17609d75177c47d9818b0f5fe24e0cb32023-11-07T01:01:37ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452022-08-01541314132410.3724/abbs.202209920d259ccNicotinamide mononucleotide improves spermatogenic function in streptozotocin-induced diabetic mice via modulating the glycolysis pathwayMa Duo0Hu Linlin1Wang Jinyuan2Luo Min3Liang Aihong4Lei Xiaocan5Liao Biyun6Li Meixiang7Xie Ming8Li Haicheng9Gong Yiwei10Zi Dan11Li Xiangrun12Chen Xi13Liao Xucai14["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","Institute of Clinical Anatomy & Reproductive Medicine, Hengyang Medical School, University of South China, Hengyang 421001, China"]["Reproductive Medicine Center, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, China"]["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","Institute of Clinical Anatomy & Reproductive Medicine, Hengyang Medical School, University of South China, Hengyang 421001, China"]["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","Institute of Clinical Anatomy & Reproductive Medicine, Hengyang Medical School, University of South China, Hengyang 421001, China"]["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","Institute of Clinical Anatomy & Reproductive Medicine, Hengyang Medical School, University of South China, Hengyang 421001, China"]["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","Institute of Clinical Anatomy & Reproductive Medicine, Hengyang Medical School, University of South China, Hengyang 421001, China"]["Reproductive Medicine Center, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, China"]["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","Institute of Clinical Anatomy & Reproductive Medicine, Hengyang Medical School, University of South China, Hengyang 421001, China"]["Institute of Clinical Anatomy & Reproductive Medicine, Hengyang Medical School, University of South China, Hengyang 421001, China"]["Institute of Clinical Anatomy & Reproductive Medicine, Hengyang Medical School, University of South China, Hengyang 421001, China"]["Institute of Clinical Anatomy & Reproductive Medicine, Hengyang Medical School, University of South China, Hengyang 421001, China"]["Institute of Clinical Anatomy & Reproductive Medicine, Hengyang Medical School, University of South China, Hengyang 421001, China"]["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"]["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","Institute of Clinical Anatomy & Reproductive Medicine, Hengyang Medical School, University of South China, Hengyang 421001, China"]["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"]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 spermatogenic dysfunction. https://www.sciengine.com/doi/10.3724/abbs.2022099nicotinamide mononucleotidediabetesspermatogenic functionSertoli cellglycolysis
spellingShingle Ma Duo
Hu Linlin
Wang Jinyuan
Luo Min
Liang Aihong
Lei Xiaocan
Liao Biyun
Li Meixiang
Xie Ming
Li Haicheng
Gong Yiwei
Zi Dan
Li Xiangrun
Chen Xi
Liao Xucai
Nicotinamide mononucleotide improves spermatogenic function in streptozotocin-induced diabetic mice via modulating the glycolysis pathway
Acta Biochimica et Biophysica Sinica
nicotinamide mononucleotide
diabetes
spermatogenic function
Sertoli cell
glycolysis
title Nicotinamide mononucleotide improves spermatogenic function in streptozotocin-induced diabetic mice via modulating the glycolysis pathway
title_full Nicotinamide mononucleotide improves spermatogenic function in streptozotocin-induced diabetic mice via modulating the glycolysis pathway
title_fullStr Nicotinamide mononucleotide improves spermatogenic function in streptozotocin-induced diabetic mice via modulating the glycolysis pathway
title_full_unstemmed Nicotinamide mononucleotide improves spermatogenic function in streptozotocin-induced diabetic mice via modulating the glycolysis pathway
title_short Nicotinamide mononucleotide improves spermatogenic function in streptozotocin-induced diabetic mice via modulating the glycolysis pathway
title_sort nicotinamide mononucleotide improves spermatogenic function in streptozotocin induced diabetic mice via modulating the glycolysis pathway
topic nicotinamide mononucleotide
diabetes
spermatogenic function
Sertoli cell
glycolysis
url https://www.sciengine.com/doi/10.3724/abbs.2022099
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