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Published on: July 16, 2021
Polystyrene microplastics disrupt the blood-testis barrier integrity through ROS-Mediated imbalance of mTORC1 and
Yuexin Wei1, Yu Zhou1, Chunlan Long2
1Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, PR China; Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, 400014, PR China; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, PR China.
Abstract:
It has been found that polystyrene microplastics (PS-MPs) exposure leads to decreased sperm quality and quantity, and we aim to explore the underlying mechanisms. Therefore, we gave 20 mg/kg body weight (bw) and 40 mg/kg bw 4 μm and 10 μm PS-MPs to male Balb/c mice by gavage. RNA sequencing of testes was performed. After PS-MPs exposure, blood-testis barrier (BTB) integrity was impaired. Since cytoskeleton was closely related to BTB integrity maintenance, and cytoskeleton disorganization could be induced by PS-MPs exposure in the testis, which resulted in the truncation of actin filaments and disruption of BTB integrity. Such processes were attributed to the differential expression of Arp3 and Eps8 (two of the most important actin-binding proteins). According to the transcriptome sequencing results, we examined the oxidative stress level in the testes and Sertoli cells. We found that PS-MPs exposure induced increased reactive oxygen species (ROS) level, which destroyed the balance between mTORC1 and mTORC2 (the mTORC1 activity was increased, while the mTORC2 activity was decreased). In conclusion, PS-MPs induced the imbalance of mTORC1 and mTORC2 via the ROS burst, and altered the expression profile of actin-binding proteins, resulting in F-actin disorganization and reduced expression of junctional proteins in the BTB. Eventually PS-MPs led to BTB integrity disruption and spermatogenesis dysfunction.
Insights
Polystyrene microplastics (PS-MPs) harm male fertility by disrupting the blood-testis barrier. This damage stems from oxidative stress and altered protein expression, leading to impaired sperm production.
Area of Science:
- Environmental Toxicology
- Reproductive Biology
- Cell Biology
Background:
- Polystyrene microplastics (PS-MPs) are environmental contaminants.
- PS-MPs exposure is linked to reduced sperm quality and quantity.
- The underlying mechanisms of PS-MP toxicity on male reproduction require elucidation.
Purpose of the Study:
- To investigate the mechanisms by which PS-MPs affect male reproductive health.
- To explore the impact of PS-MPs on blood-testis barrier (BTB) integrity and spermatogenesis.
Main Methods:
- Male Balb/c mice were exposed to varying doses and sizes of PS-MPs via gavage.
- Testicular RNA sequencing was performed to analyze gene expression changes.
- Oxidative stress levels, reactive oxygen species (ROS), and mTOR signaling pathways were assessed.
Main Results:
- PS-MPs exposure impaired BTB integrity and caused cytoskeleton disorganization.
- Differential expression of actin-binding proteins (Arp3, Eps8) was observed.
- PS-MPs induced ROS burst, leading to mTORC1/mTORC2 pathway imbalance.
- Spermatogenesis dysfunction and reduced sperm quality were noted.
Conclusions:
- PS-MPs disrupt BTB integrity by inducing oxidative stress and altering actin-binding protein expression.
- The ROS-mediated imbalance of mTORC1/mTORC2 signaling contributes to PS-MP toxicity.
- PS-MPs negatively impact male reproductive function through multiple cellular pathways.
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