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Updated: May 28, 2026
An In Vivo Method to Study Mouse Blood-Testis Barrier Integrity
Published on: December 2, 2018
PFOA Damages Blood-Testis Barrier Integrity in Mice by Inhibited Glycolysis Caused H3K18 Lactylation Modification
Zhengqi Song1,2, Jinxin Ruan1,2, Lingqiao Wang2
1The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Heath, Guizhou Medical University, Guiyang 550025, China.
Abstract:
The molecular mechanism underlying male reproductive toxicity associated with Perfluorooctanoic acid (PFOA), a persistent environmental endocrine disruptor (EDC), has not yet been fully elucidated. Six-week-old male C57BL/6 mice were treated with PFOA by oral gavage at 0, 1.25, 5, 10, and 20 mg/kg/day for 35 days to explore its toxic effects on the male reproductive system and the underlying mechanisms. Analyses of semen quality, testicular histopathology, and blood-testis barrier (BTB) integrity revealed that PFOA caused dose-dependent structural and functional damage to the BTB, leading to markedly reduced semen quality. Based on transcriptomic sequencing and differential gene enrichment analysis, the glycolytic pathway was identified as a key regulatory target for PFOA-induced damage to the reproductive system. Further validation revealed that PFOA exposure inhibited glycolysis-related enzymes (Hexokinase 1 (HK1), Glucose Transporter 1 (GLUT1), and Lactate Dehydrogenase A (LDHA)), reduced lactate production and ATP synthesis, lowered Pan-Kla and H3K18la levels, and diminished H3K18la enrichment at the Hk1, Glut1, and Ldha promoters, whereas exogenous sodium lactate reversed these changes. This study is the first to identify the "glycolysis-lactate-H3K18la" chain as a key regulator in PFOA-induced BTB damage and spermatogenesis impairment, offering a new theoretical foundation for understanding EDC-induced male reproductive toxicity.
Insights
Perfluorooctanoic acid (PFOA) damages male reproductive health by disrupting the blood-testis barrier (BTB) and impairing spermatogenesis via the glycolysis-lactate-H3K18la pathway.
Area of Science:
- Environmental Toxicology
- Reproductive Biology
- Molecular Mechanisms
Background:
- Perfluorooctanoic acid (PFOA) is a persistent environmental endocrine disruptor (EDC) linked to male reproductive toxicity.
- The precise molecular mechanisms of PFOA-induced male reproductive toxicity remain incompletely understood.
Purpose of the Study:
- To elucidate the molecular mechanisms of PFOA-induced male reproductive toxicity.
- To investigate the effects of PFOA on male reproductive system structure and function in mice.
Main Methods:
- Male C57BL/6 mice were orally administered PFOA (0-20 mg/kg/day) for 35 days.
- Evaluated semen quality, testicular histopathology, and blood-testis barrier (BTB) integrity.
- Utilized transcriptomic sequencing, gene enrichment analysis, and biochemical assays to identify key molecular pathways and targets.
Main Results:
- PFOA exposure caused dose-dependent damage to the BTB, leading to reduced semen quality.
- Transcriptomic analysis identified the glycolytic pathway as a critical target of PFOA toxicity.
- PFOA inhibited key glycolysis enzymes (HK1, GLUT1, LDHA), reduced ATP and lactate production, and altered H3K18la levels, impacting gene promoter enrichment.
Conclusions:
- The study identifies a novel "glycolysis-lactate-H3K18la" regulatory axis in PFOA-induced BTB damage and impaired spermatogenesis.
- This finding provides a new theoretical framework for understanding EDC-induced male reproductive toxicity.
- Exogenous sodium lactate partially reversed PFOA-induced toxic effects.
