Polyamine metabolism links gut microbiota and testicular dysfunction
Qi Zhao1,2, Jian-Feng Huang2,3, Yan Cheng1
1Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
Background:
Male fertility impaired by exogenous toxins is a serious worldwide issue threatening the health of the new-born and causing infertility. However, the metabolic connection between toxic exposures and testicular dysfunction remains unclear.
Results:
In the present study, the metabolic disorder of testicular dysfunction was investigated using triptolide-induced testicular injury in mice. We found that triptolide induced spermine deficiency resulting from disruption of polyamine biosynthesis and uptake in testis, and perturbation of the gut microbiota. Supplementation with exogenous spermine reversed triptolide-induced testicular dysfunction through increasing the expression of genes related to early and late spermatogenic events, as well as increasing the reduced number of offspring. Loss of gut microbiota by antibiotic treatment resulted in depletion of spermine levels in the intestine and potentiation of testicular injury. Testicular dysfunction in triptolide-treated mice was reversed by gut microbial transplantation from untreated mice and supplementation with polyamine-producing Parabacteroides distasonis. The protective effect of spermine during testicular injury was largely dependent on upregulation of heat shock protein 70s (HSP70s) both in vivo and in vitro.
Conclusions:
The present study linked alterations in the gut microbiota to testicular dysfunction through disruption of polyamine metabolism. The diversity and dynamics of the gut microbiota may be considered as a therapeutic option to prevent male infertility. Video Abstract.
Insights
Toxic exposures impair male fertility by disrupting gut microbiota and spermine levels. Restoring spermine or gut bacteria can reverse testicular dysfunction and improve fertility, offering new therapeutic strategies.
Area of Science:
- Reproductive Biology
- Microbiology
- Toxicology
Background:
- Male infertility due to environmental toxins is a global health concern.
- The metabolic pathways linking toxin exposure to testicular damage are not fully understood.
Purpose of the Study:
- To investigate the metabolic basis of triptolide-induced testicular dysfunction.
- To explore the role of polyamine metabolism and gut microbiota in male reproductive health.
Main Methods:
- Induction of testicular injury in mice using triptolide.
- Analysis of polyamine levels, gut microbiota composition, and gene expression.
- Intervention with exogenous spermine, antibiotics, microbial transplantation, and specific bacteria.
Main Results:
- Triptolide caused spermine deficiency and gut microbiota imbalance, leading to testicular dysfunction.
- Exogenous spermine supplementation or gut microbiota restoration (transplantation or Parabacteroides distasonis) reversed the injury.
- Spermine's protective effect involved upregulating heat shock protein 70s (HSP70s).
Conclusions:
- Gut microbiota alterations disrupt polyamine metabolism, contributing to male infertility.
- Modulating gut microbiota and polyamine levels presents a potential therapeutic approach for male infertility.
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