Substance P restores spermatogenesis in busulfan-treated mice: A new strategy for male infertility therapy
Substance P restores spermatogenesis in busulfan-treated mice: A new strategy for male infertility therapy
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P物质恢复白消安治疗小鼠的精子发生：男性不育症治疗的新策略
DOI：
10.1016/j.biopha.2020.110868
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发表时间：
2021-01-01
影响因子：
7.5
通讯作者：
Jiang, Mei Hua
中科院分区：
文献类型：
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作者：
Chen, Zhihong;Liu, Minjie;Jiang, Mei Hua
男性不育已成为一个重要的健康问题，主要是由睾丸功能障碍与精子发生异常引起的。在这项研究中，我们证明了神经肽，P物质（SP），是必不可少的精原细胞增殖曲细精管培养系统。此外，SP（5 nmol/kg）处理显著恢复了白消安诱导的非梗阻性无精子症小鼠模型的精子发生，改善了精子质量，并增加了ZBTB 16（+）或LIN 28（+）未分化精原细胞以及STRA 8（+）分化精原细胞的数量。此外，100 nM SP处理在体外显着刺激GC-1 spg细胞（精原细胞系）的增殖，通过激活Erk 1/2信号通路。此外，经选择性NK-1受体拮抗剂RP 67580处理后，精子质量和精原细胞数量显著降低，表明SP-NK 1 R信号在精子发生中起重要作用。综上所述，这些结果表明，SP可能是一种潜在的治疗剂，通过加速精子发生的恢复男性不育症。
Male infertility has become an important health problem that is primarily caused by testicular dysfunction with abnormal spermatogenesis. In this study, we demonstrated that the neuropeptide, substance P (SP), is essential for spermatogonia proliferation in a seminiferous tubule culture system. In addition, SP (5 nmol/kg) treatment markedly restored spermatogenesis, improved sperm quality, and increased the number of ZBTB16(+) or LIN28(+) undifferentiated spermatogonia as well as STRA8(+) differentiated spermatogonia in a busulfan-induced non-obstructive azoospermic mouse model. Furthermore, 100 nM SP treatment in vitro significantly stimulated the proliferation of GC-1 spg cells (a spermatogonia cell line) via activation of the Erk1/2 signaling pathway. Moreover, the sperm quality and the number of spermatogonia were significantly reduced after treatment with RP67580, a selective NK-1 receptor antagonist, suggesting that SP-NK1R signaling plays an important role in spermatogenesis. Taken together, these results suggest that SP may be a potential therapeutic agent for male infertility by accelerating the restoration of spermatogenesis.