title: Melatonin Ameliorates Busulfan-Induced Spermatogonial Stem Cell Oxidative Apoptosis in Mouse Testes.
abstract: Many men endure immunosuppressive or anticancer treatments that contain alkylating agents before the age of sexual maturity, especially the increasing number of preadolescent males who undergo busulfan treatment for myeloablative conditioning before hematopoietic stem cell transplantation. Before sperm production, there are no sperm available for cryopreservation. Thus, it is necessary to identify a solution to ameliorate the busulfan-induced damage of spermatogonial stem cells (SSCs).
  
  
  
  In this study, we demonstrated that melatonin relieved the previously described SSC loss and apoptosis in mouse testes. Melatonin increased the expression of manganese superoxide dismutase (MnSOD), which regulated the production of busulfan-induced reactive oxygen species (ROS). Moreover, melatonin promoted sirtuin type 1 (SIRT1) expression. SIRT1 participated in the deacetylation of p53, which promotes p53 ubiquitin degradation. Decreased concentrations of deacetylated p53 resulted in spermatogonial cell resistance to apoptosis. Acute T cell leukemia cell assay demonstrated that melatonin does not affect busulfan-induced cancer cell apoptosis and ROS.
  
  
  
  The current evidence suggests that melatonin may alleviate the side effects of alkylating drugs, such as busulfan.
  
  
  
  Melatonin promoted MnSOD and SIRT1 expression, which successfully ameliorated busulfan-induced SSC apoptosis caused by high concentrations of ROS and p53. Antioxid. Redox Signal. 28, 385-400.
authors.affiliation: 1 College of Veterinary Medicine, Shaanxi Centre of Stem Cell Engineering and Technology, Northwest A&F University , Yangling, Shaanxi, China .
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: 1 College of Veterinary Medicine, Shaanxi Centre of Stem Cell Engineering and Technology, Northwest A&F University , Yangling, Shaanxi, China .
authors.forename: Xin
authors.initials: X
authors.lastname: He
authors.affiliation: 1 College of Veterinary Medicine, Shaanxi Centre of Stem Cell Engineering and Technology, Northwest A&F University , Yangling, Shaanxi, China .
authors.forename: Mengru
authors.initials: M
authors.lastname: Zhuang
authors.affiliation: 1 College of Veterinary Medicine, Shaanxi Centre of Stem Cell Engineering and Technology, Northwest A&F University , Yangling, Shaanxi, China .
authors.forename: Bowen
authors.initials: B
authors.lastname: Niu
authors.affiliation: 1 College of Veterinary Medicine, Shaanxi Centre of Stem Cell Engineering and Technology, Northwest A&F University , Yangling, Shaanxi, China .
authors.forename: Chongyang
authors.initials: C
authors.lastname: Wu
authors.affiliation: 1 College of Veterinary Medicine, Shaanxi Centre of Stem Cell Engineering and Technology, Northwest A&F University , Yangling, Shaanxi, China .
authors.forename: Hailong
authors.initials: H
authors.lastname: Mu
authors.affiliation: 1 College of Veterinary Medicine, Shaanxi Centre of Stem Cell Engineering and Technology, Northwest A&F University , Yangling, Shaanxi, China .
authors.forename: Furong
authors.initials: F
authors.lastname: Tang
authors.affiliation: 1 College of Veterinary Medicine, Shaanxi Centre of Stem Cell Engineering and Technology, Northwest A&F University , Yangling, Shaanxi, China .
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Cui
authors.affiliation: 3 Department of Pathology, Yangling Demonstration Zone Hospital , Yangling, Shaanxi, China .
authors.forename: Weishuai
authors.initials: W
authors.lastname: Liu
authors.affiliation: 1 College of Veterinary Medicine, Shaanxi Centre of Stem Cell Engineering and Technology, Northwest A&F University , Yangling, Shaanxi, China .
authors.forename: Baoyu
authors.initials: B
authors.lastname: Zhao
authors.affiliation: 1 College of Veterinary Medicine, Shaanxi Centre of Stem Cell Engineering and Technology, Northwest A&F University , Yangling, Shaanxi, China .
authors.forename: Sha
authors.initials: S
authors.lastname: Peng
authors.affiliation: 2 Key Laboratory for Mammalian Reproductive Biology and Biotechnology, Ministry of Education, Inner Mongolia University , Hohhot, China .
authors.forename: Guangpeng
authors.initials: G
authors.lastname: Li
authors.affiliation: 1 College of Veterinary Medicine, Shaanxi Centre of Stem Cell Engineering and Technology, Northwest A&F University , Yangling, Shaanxi, China .
authors.forename: Jinlian
authors.initials: J
authors.lastname: Hua
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002066:Busulfan / Q000009:adverse effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D008297:Male; D008550:Melatonin / Q000008:administration & dosage*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D056564:Sirtuin 1 / Q000235:genetics*; D013093:Spermatogonia / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D013234:Stem Cells / Q000187:drug effects / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics*; D013737:Testis / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025801:Ubiquitin / Q000235:genetics
chemical_list: D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; D013482:Superoxide Dismutase; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D002066:Busulfan; D008550:Melatonin
keywords: ROS (reactive oxygen species); SSCs (spermatogonial stem cells); apoptosis; busulfan; melatonin; p53