2. Academic Validation
  3. Long-term exposure to low concentrations of MC-LR induces blood-testis barrier damage through the RhoA/ROCK pathway

Long-term exposure to low concentrations of MC-LR induces blood-testis barrier damage through the RhoA/ROCK pathway

  • Ecotoxicol Environ Saf. 2022 May 1;236:113454. doi: 10.1016/j.ecoenv.2022.113454.
Haohao Liu 1,  Xin Zeng 1,  Ya Ma 1,  Xinghai Chen 2,  Michael D Losiewicz 2,  Xingde Du 1,  Zhihui Tian 1,  Shiyu Zhang 1,  Linjia Shi 1,  Huizhen Zhang 3,  Fei Yang 4
Affiliations

Affiliations

  • 1 College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China.
  • 2 Department of Chemistry and Biochemistry, St Mary's University, San Antonio, TX, USA.
  • 3 College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China. Electronic address: [email protected].
  • 4 Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China; Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha 410008, Hunan, China. Electronic address: [email protected].
PMID: 35367887 DOI: 10.1016/j.ecoenv.2022.113454
Abstract

Microcystin-leucine arginine (MC-LR), an emerging water pollutant, produced by cyanobacteria, has an acute testicular toxicity. However, little is known about the chronic toxic effects of MC-LR exposure on the testis at environmental concentrations and the underlying molecular mechanisms. In this study, C57BL/6 J mice were exposed to different low concentrations of MC-LR for 6, 9 and 12 months. The results showed that MC-LR could cause testis structure loss, cell abscission and blood-testis barrier (BTB) damage. Long-term exposure of MC-LR also activated RhoA/ROCK pathway, which was accompanied by the rearrangement of α-Tubulin. Furthermore, MC-LR reduced the levels of the adherens junction proteins (N-Cadherin and β-catenin) and the tight junction proteins (ZO-1 and Occludin) in a dose- and time-dependent way, causing BTB damage. MC-LR also reduced the expressions of Occludin, ZO-1, β-catenin, and N-Cadherin in TM4 cells, accompanied by a disruption of cytoskeletal proteins. More importantly, the RhoA inhibitor Rhosin ameliorated these MC-LR-induced changes. Together, these new findings suggest that long-term exposure to MC-LR induces BTB damage through RhoA/ROCK activation: involvement of tight junction and adherens junction changes and Cytoskeleton disruption. This study highlights a new mechanism for MC-LR-induced BTB disruption and provides new insights into the cause and treatment of BTB disruption.

Keywords

Adherens junction changes; BTB damages; Cytoskeleton rearrangement; Microcystin-leucine arginine; Reproductive toxicity; Water pollution.

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