Related Experiment Video
Updated: Feb 22, 2026
Purification of Transcripts and Metabolites from Drosophila Heads
Published on: March 15, 2013
Single-cell transcriptomics reveals the toxic mechanism and therapeutic target of ubiquitously distributed mycotoxin
Wuwen Feng1, Dandan Zhang2, Hui Feng2
1Chinese Medicine Germplasm Resources Innovation and Effective Uses Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Key Laboratory of the Ministry of Education for Standardization of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Background:
Deoxynivalenol (DON), a prevalent mycotoxin contaminating herbal medicines and daily diets, poses significant threats to male reproductive health, yet dissection of its testicular toxicity at single cell resolution remains unexplored.
Purpose:
Herein, we integrated single-cell RNA sequencing (scRNA-seq) with functional analyses to characterize the cellular and molecular features of DON-induced testicular toxicity.
Methods:
The toxicity of DON was evaluated by morphology, organ index, sex hormones, sperm morphology and quantity, and H&E staining. scRNA-seq was used to dissect the cellular and molecular mechanisms of DON-induced testicular injury. Nuclear spreading immunostaining, Western blot, and supplement of inhibitor were used to confirm the toxic mechanism of DON.
Results:
In sexually mature rats, chronic DON exposure caused dose-dependent testicular structural damage, hormonal imbalance, and impaired sperm quality. scRNA-seq of 70,000 testicular cells revealed DON-driven aberrant accumulation of early spermatocytes. Further analysis indicated defective meiotic progression at the leptotene stage, accompanied by suppressed homologous recombination-related genes including Brca2 and Rad51, and disrupted chromosome pairing. SCENIC regulatory network analysis suggested that KDM5A is functionally associated with leptotene spermatocyte maturation, and its activity was inhibited by DON. Notably, pharmacological activation of KDM5A using agonist D18 reversed the pathological decrease of BRCA2 and RAD51, partially rescued meiotic progression, and ameliorated sperm defects in DON-exposed models.
Conclusion:
Our study establishes the first single-cell atlas of DON-induced testicular injury and identifies KDM5A as a critical component of the regulatory network disrupted during mycotoxin-impaired spermatogenesis. These findings provide mechanistic insights into mycotoxin-related male infertility and highlight a potential therapeutic avenue for its mitigation.
Insights
Deoxynivalenol (DON) mycotoxin exposure damages male fertility by disrupting spermatocyte development. Activating KDM5A partially restores sperm quality and meiotic progression, offering a potential therapeutic strategy for male infertility.
Area of Science:
- Reproductive Toxicology
- Molecular Biology
- Genomics
Background:
- Deoxynivalenol (DON) is a widespread mycotoxin found in food and herbal medicines.
- DON exposure poses risks to male reproductive health, but its specific testicular toxicity mechanisms at the single-cell level are not well understood.
Purpose of the Study:
- To investigate the cellular and molecular impacts of DON-induced testicular toxicity using single-cell RNA sequencing (scRNA-seq).
- To identify key molecular pathways and potential therapeutic targets involved in DON-related male infertility.
Main Methods:
- Comprehensive evaluation of DON toxicity including morphology, hormone levels, sperm parameters, and histology.
- scRNA-seq analysis of approximately 70,000 testicular cells to identify cell types affected by DON.
- Functional assays, Western blotting, and pharmacological interventions to elucidate and validate DON's toxic mechanisms.
Main Results:
- Chronic DON exposure in rats led to testicular damage, hormonal imbalance, and reduced sperm quality in a dose-dependent manner.
- scRNA-seq identified aberrant accumulation of early spermatocytes and defective meiotic progression at the leptotene stage.
- DON suppressed key homologous recombination genes (e.g., Brca2, Rad51) and inhibited KDM5A activity, crucial for spermatocyte maturation. Pharmacological activation of KDM5A partially reversed these effects.
Conclusions:
- This study presents the first single-cell atlas of DON-induced testicular injury, revealing disrupted spermatogenesis.
- KDM5A is identified as a critical factor in the regulatory network affected by DON, highlighting its role in mycotoxin-induced male infertility.
- Targeting KDM5A may offer a therapeutic approach to mitigate mycotoxin-related male reproductive dysfunction.
More Related Videos
05:45Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells
Published on: October 10, 2025
09:44RNAi-mediated Control of Aflatoxins in Peanut: Method to Analyze Mycotoxin Production and Transgene Expression in the Peanut/Aspergillus Pathosystem
Published on: December 21, 2015
Related Concept Videos
01:23Toxicity Testing in Animals
01:25Bioactivation and Tissue Toxicity
01:00Drug Toxicity: Overview
01:06Induced Pluripotent Stem Cells
Somatic...
01:22MicroRNAs