期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 133, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2020.110868
关键词
Spermatogenesis; Substance P; Male infertility; Endogenous spermatogonia
资金
- National Key Research and Development Program of China [2017YFA0103802]
- National Natural Science Foundation of China [31972894, 81770290]
- Science and Technology Planning Project of Guangdong Province [2016B030229006, 2014A020211007, 2016B030230001]
- Key Scientific and Technological Program of Guangzhou City [201604020158, 201604020189]
The study demonstrates that the neuropeptide substance P plays a crucial role in spermatogonia proliferation and can potentially serve as a therapeutic agent for male infertility by accelerating the restoration of spermatogenesis.
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.
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