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Published on: May 4, 2020
Effects of Excessive Manganese Exposure on Testicular Oxidative Stress, Histopathology, and Nrf2 Signaling Pathway in
Dianyi Peng1, Fuqing Feng1, Heng Yin1
1College of Life Sciences and Agri-forestry, Southwest University of Science and Technology, Mianyang, 621010, China.
Abstract:
Manganese, an essential trace element critical for maintaining normal physiological functions in living organisms, may exert adverse health effects under conditions of excessive exposure. The present study sought to investigate the impact of manganese exposure on mouse testicular tissue and elucidate the underlying mechanisms. Male ICR mice were administered graded doses of manganese chloride (MnCl₂) via oral gavage. The extent of testicular injury was assessed through histopathological examination, while oxidative stress levels were quantified using biochemical assay kits. The expression of key proteins and mRNA involved in the Nrf2 signaling pathway was evaluated by immunofluorescence, Western blotting, and real-time quantitative PCR. The results demonstrated that manganese exposure induced pathological damage in testicular tissue, triggered oxidative stress responses, and significantly reduced antioxidant capacity. Further mechanistic analysis revealed that manganese exposure downregulated the protein and mRNA expression levels of Nrf2, HO-1, and NQO-1, concurrently upregulated Keap1 expression, and suppressed Nrf2 nuclear translocation. In summary, manganese exposure can cause testicular tissue damage. This is associated with oxidative stress and inhibition of the Nrf2 signaling pathway.
Insights
Excessive manganese exposure damages mouse testicular tissue by inducing oxidative stress and inhibiting the Nrf2 signaling pathway, impacting antioxidant capacity and key protein expression.
Area of Science:
- Toxicology
- Reproductive Biology
- Cellular Signaling
Background:
- Manganese is essential but toxic at high levels.
- Understanding manganese toxicity mechanisms is crucial for health.
- Testicular function is sensitive to environmental exposures.
Purpose of the Study:
- Investigate manganese's impact on mouse testicular tissue.
- Elucidate the mechanisms of manganese-induced testicular injury.
- Assess the role of the Nrf2 signaling pathway.
Main Methods:
- Oral administration of manganese chloride to male ICR mice.
- Histopathological examination for testicular damage.
- Biochemical assays for oxidative stress and antioxidant capacity.
- Immunofluorescence, Western blotting, and qPCR for Nrf2 pathway analysis.
Main Results:
- Manganese exposure caused significant testicular pathological damage.
- Increased oxidative stress and reduced antioxidant capacity were observed.
- Downregulation of Nrf2, HO-1, and NQO-1, and upregulation of Keap1 were noted.
- Suppressed Nrf2 nuclear translocation indicated pathway inhibition.
Conclusions:
- Manganese exposure induces testicular damage.
- Oxidative stress and Nrf2 pathway inhibition are key mechanisms.
- Findings highlight the reproductive risks of manganese toxicity.