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Published on: December 28, 2021
In vitro toxicity evaluation of melamine on mouse TM4 Sertoli cells
Lingling Chang1, Jingyuan Wang2, Ruiping She2
1College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, PR China; Laboratory of Animal Pathology and Public Health, Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agriculture University, Beijing, PR China.
Abstract:
The male reproductive toxicity of melamine (MA) has been recognized in recent years excepted for its renal toxicity. Our previous in vivo studies revealed that the damages of Sertoli cell barrier played a critical role in MA-induced testicular toxicity in mice. Herein, we performed an in vitro study to comprehensively evaluate the toxicity of MA on Sertoli cell by examining the influences of MA on the viability, morphology, mortality and intercellular junctions of mouse TM4 Sertoli cells (TM4 cells). The results showed that MA suppressed cell viability, induced obvious ultrastructural changes and cell apoptosis in concentration-dependent manner. Moreover, MA down-regulated the expressions of junction-associated proteins including occludin, N-cadherin, and vimentin, suggesting that MA disrupted the integrity of Sertoli cell barrier. Thus, these results indicated that Sertoli cell might be an important cellular target for MA-induced male reproductive toxicity.
Insights
Melamine (MA) harms male reproductive health by damaging Sertoli cells, crucial for testicular function. This study confirms MA disrupts Sertoli cell viability and barrier integrity, highlighting them as a key target in MA toxicity.
Area of Science:
- Reproductive Toxicology
- Cell Biology
- Environmental Health
Background:
- Melamine (MA) is known for renal toxicity, but its male reproductive toxicity is increasingly recognized.
- Previous in vivo studies implicated Sertoli cell barrier damage in MA-induced testicular toxicity.
Purpose of the Study:
- To investigate the in vitro toxicity of melamine (MA) on mouse TM4 Sertoli cells.
- To evaluate MA's effects on Sertoli cell viability, morphology, mortality, and intercellular junction integrity.
Main Methods:
- Exposure of mouse TM4 Sertoli cells to varying concentrations of MA.
- Assessment of cell viability, morphology, apoptosis, and expression of junction-associated proteins (occludin, N-cadherin, vimentin).
Main Results:
- MA significantly suppressed Sertoli cell viability and induced apoptosis in a dose-dependent manner.
- Ultrastructural changes and disruption of intercellular junctions were observed.
- MA down-regulated key proteins (occludin, N-cadherin, vimentin) essential for barrier integrity.
Conclusions:
- Sertoli cells are a primary cellular target for melamine-induced male reproductive toxicity.
- MA disrupts the Sertoli cell barrier by affecting cell viability and junctional protein expression.
- These findings provide in vitro evidence supporting the role of Sertoli cell damage in MA's reproductive toxicity.
