The neuropeptide substance P restored spermatogenesis and improved sperm quality in a mouse model of chemotherapy-induced infertility by stimulating spermatogonia proliferation through ERK1/2 signaling.
Spermatogenesis restoredSP at 5 nmol/kg markedly restored sperm production in busulfan-induced azoospermic mice
What the researchers found
Substance P at 5 nmol/kg restored spermatogenesis in busulfan-treated azoospermic mice by stimulating spermatogonia proliferation via NK1R-ERK1/2 signaling.
Why it matters
Male infertility due to chemotherapy is a growing concern as cancer survival improves. Finding that a known neuropeptide can restore sperm production opens a potential new therapeutic approach for chemotherapy-induced infertility.
The numbers in context
5 nmol/kg SP; increased ZBTB16+, LIN28+, STRA8+ spermatogonia; 100 nM SP stimulated proliferation via ERK1/2; RP67580 blocked effect
How the study worked
Busulfan-induced non-obstructive azoospermia mouse model. SP treatment (5 nmol/kg). In vitro seminiferous tubule culture and GC-1 spg cell line proliferation assays. NK-1R antagonist (RP67580) studies. Spermatogonia markers: ZBTB16+, LIN28+, STRA8+.
Who was studied
Busulfan-induced azoospermic mice and GC-1 spg spermatogonia cell line
What this study cannot tell us
Mouse model — may not directly translate to humans. Busulfan-induced azoospermia is one specific cause of infertility. Long-term effects and offspring health not assessed. Small study implied by model system.
How to read the evidence
Well-designed preclinical study with both in vivo and in vitro validation and receptor antagonist confirmation. Pre-clinical evidence.
When this study was published
Published in 2021, revealing a novel reproductive function of substance P.
The bigger picture
Substance P has been primarily studied in pain and inflammation, but this surprising fertility role reveals an entirely new function for this neuropeptide. It suggests the nervous system plays a more direct role in reproductive function than previously appreciated.
Questions still open
- Could substance P or NK-1R agonists help cancer survivors with chemotherapy-induced infertility?
- Is substance P involved in other types of male infertility?
- Would there be pain-related side effects from substance P therapy at these doses?
Common questions
Can a pain-related peptide really help with infertility?
Could this help cancer survivors who became infertile from treatment?
Read the original research
Substance P restores spermatogenesis in busulfan-treated mice: A new strategy for male infertility therapy.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 133, 110868
Citation
Chen, Zhihong; Liu, Minjie; Hu, Jin-Hua; Gao, Yong; Deng, Chunhua; Jiang, Mei Hua. (2021). Substance P restores spermatogenesis in busulfan-treated mice: A new strategy for male infertility therapy.. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 133, 110868. https://doi.org/10.1016/j.biopha.2020.110868