Substance P Restores Sperm Production in Infertile Mice

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.

Chen, Zhihong et al.·Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie·2021·Preliminary Evidenceanimal
RPEP-05318AnimalPreliminary Evidence2021RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
animal
Evidence
Preliminary Evidence
Sample
N=not reported
Participants
Busulfan-induced azoospermic mice and GC-1 spg spermatogonia cell line

What This Study Found

Substance P at 5 nmol/kg restored spermatogenesis in busulfan-treated azoospermic mice by stimulating spermatogonia proliferation via NK1R-ERK1/2 signaling.

Key Numbers

5 nmol/kg SP; increased ZBTB16+, LIN28+, STRA8+ spermatogonia; 100 nM SP stimulated proliferation via ERK1/2; RP67580 blocked effect

How They Did This

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+.

Why This Research 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 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.

What This Study Doesn't 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.

Questions This Raises

  • ?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?

Trust & Context

Key Stat:
Spermatogenesis restored SP at 5 nmol/kg markedly restored sperm production in busulfan-induced azoospermic mice
Evidence Grade:
Well-designed preclinical study with both in vivo and in vitro validation and receptor antagonist confirmation. Pre-clinical evidence.
Study Age:
Published in 2021, revealing a novel reproductive function of substance P.
Original Title:
Substance P restores spermatogenesis in busulfan-treated mice: A new strategy for male infertility therapy.
Published In:
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 133, 110868 (2021)
Database ID:
RPEP-05318

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study
What do these levels mean? →

Frequently Asked Questions

Can a pain-related peptide really help with infertility?

Surprisingly, yes. Substance P, best known for transmitting pain signals, was found to stimulate the proliferation of sperm precursor cells. In mice made infertile by chemotherapy, substance P treatment restored sperm production and improved sperm quality.

Could this help cancer survivors who became infertile from treatment?

It's a promising possibility. This study shows that substance P can restart sperm production in mice after chemotherapy-induced sterility. If similar results are found in humans, it could offer a new treatment for one of the most distressing side effects of cancer therapy.

Read More on RethinkPeptides

Cite This Study

RPEP-05318·https://rethinkpeptides.com/research/RPEP-05318

APA

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

MLA

Chen, Zhihong, et al. "Substance P restores spermatogenesis in busulfan-treated mice: A new strategy for male infertility therapy.." Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2021. https://doi.org/10.1016/j.biopha.2020.110868

RethinkPeptides

RethinkPeptides Research Database. "Substance P restores spermatogenesis in busulfan-treated mic..." RPEP-05318. Retrieved from https://rethinkpeptides.com/research/chen-2021-substance-p-restores-spermatogenesis

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.