Acta Veterinaria et Zootechnica Sinica ›› 2024, Vol. 55 ›› Issue (6): 2486-2497.doi: 10.11843/j.issn.0366-6964.2024.06.020

• Animal Biotechnology and Reproduction • Previous Articles     Next Articles

Study on the Mechanism of Melatonin Relieving Testicular Damage in Mice Induced Busulfan

Kaihui WU1(), Liuguang ZHANG2, Chao WANG1,3, Shiyuan XU1,3, Songqi LIU1, Kaimin YUAN1,3, Dong WANG1,*(), Yunwei PANG1,*()   

  1. 1. Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
    2. Center for Reproductive Medicine, Haikou Mary Hospital, Haikou 570203, China
    3. College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China
  • Received:2023-11-14 Online:2024-06-23 Published:2024-06-28
  • Contact: Dong WANG, Yunwei PANG E-mail:2840259661@qq.com;dwangcn2002@vip.sina.com;pangyunwei@caas.cn

Abstract:

The study aimed to reveal the mechanism of melatonin in alleviating testicular damage caused by busulfan, improve the efficiency of busulfan in preparing spermatogonial stem cell transplantation recipients, and explore its therapeutic effect on male spermatogenic function caused by busulfan's toxicity. In this study, ICR male mice at 6-7 weeks were used as model animals and divided into control group, busulfan treatment group, and busulfan+melatonin treatment group. Each group had 8 replicates and samples were taken on the 7th day after injection. The levels of inflammatory cytokines in testicular tissue was detected using ELISA, and perform HE staining on the testes and epididymis. In addition, immunohistochemistry or immunofluorescence were used to detect the expression of blood testis barrier related proteins to analyze the effect of melatonin on BTB. The results showed that after injection of busulfan into mice, combined with melatonin treatment, the trend of decreased testicular weight and testicular body rate was significantly alleviated, and the rate of decrease in sperm count was slowed down; HE staining of testicular tissue and detection of inflammatory cytokines showed that melatonin significantly slowed down the upward trend of nuclear transportation factor κB, p-NF-κB, interleukin-1β, tumor necrosis factor-α and myeloperoxidase, thereby reducing the infiltration of inflammatory cells in the tissue; immunohistochemical or immunofluorescence detection showed that melatonin slowed down the decrease in the levels of blood testis barrier constituent proteins (Occludin, connexin-43, N-cadherin) and cytoskeletal proteins (F-actin and Vimentin) caused by busulfan treatment. Melatonin alleviates the mouse orchitis response induced by busulfan by down regulating the levels of inflammatory cytokines in testicular tissue; and by slowing down the decreasing trend of BTB related proteins content, the damage of busulfan to BTB and sertoli cells is alleviated, thereby alleviating the damage to mouse spermatogenic functionn

Key words: melatonin, busulfan, orchitis, blood testis barrier, cytoskeleton

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