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Substance P restores spermatogenesis in busulfan-treated mice: A new strategy for male infertility therapy.
- Source :
-
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2021 Jan; Vol. 133, pp. 110868. Date of Electronic Publication: 2020 Nov 09. - Publication Year :
- 2021
-
Abstract
- 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 <superscript>+</superscript> or LIN28 <superscript>+</superscript> undifferentiated spermatogonia as well as STRA8 <superscript>+</superscript> 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.<br /> (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Subjects :
- Animals
Apoptosis drug effects
Azoospermia chemically induced
Azoospermia metabolism
Azoospermia physiopathology
Busulfan
Cell Line
Cell Proliferation drug effects
Disease Models, Animal
Extracellular Signal-Regulated MAP Kinases metabolism
Male
Mice, Inbred C57BL
Receptors, Neurokinin-1 agonists
Receptors, Neurokinin-1 metabolism
Signal Transduction
Spermatogonia metabolism
Tissue Culture Techniques
Mice
Azoospermia drug therapy
Fertility drug effects
Fertility Agents, Male pharmacology
Spermatogenesis drug effects
Spermatogonia drug effects
Substance P pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1950-6007
- Volume :
- 133
- Database :
- MEDLINE
- Journal :
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
- Publication Type :
- Academic Journal
- Accession number :
- 33181455
- Full Text :
- https://doi.org/10.1016/j.biopha.2020.110868