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Updated: Feb 7, 2026

An In Vivo Method to Study Mouse Blood-Testis Barrier Integrity
Published on: December 2, 2018
Melamine causes testicular toxicity by destroying blood-testis barrier in piglets
Lingling Chang1, Zheng Lu1, Delong Li1
1College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.
Abstract:
Melamine (MA) exposure causes male reproductive toxicity, however, the mechanism remains unclear. In this study, we investigated the roles of the blood-testis barrier (BTB) in MA-induced reproductive toxicity in piglets. Male weaned piglets were exposed to MA concentrations of 0, 100, 300, and 1000 mg/kg in the diet for 10 weeks. They were euthanized on days 1, 7 and 14 after the final exposure. Body and organ weights, serum biochemistry and testosterone, gross and histopathological changes, and BTB ultrastructure and integrity were assessed. BTB junction protein expression levels and protein levels of the mitogen-activated protein kinase (MAPK) pathway in testes were measured. We found that MA dose-dependently decreased serum testosterone levels and caused gross and histopathological lesions in the testis and epididymis. Marked BTB damage was evidenced by abnormal changes in BTB ultrastructure and increased BTB permeability. Furthermore, MA decreased the protein levels of ZO-1, occludin, N-cadherin, and connexin-43, paralleled by increased the protein levels of p-Erk, p-JNK and p-p38 in testes, suggesting that MA disrupted BTB by downregulating the expressions of BTB junction proteins, with possible involvement of the MAPK signaling pathway. In conclusion, MA exposure gives rise to testicular toxicity in male piglets through destroying BTB integrity.
Insights
Melamine (MA) exposure damages the blood-testis barrier (BTB) in male piglets, leading to testicular toxicity. This disruption affects reproductive health by altering key proteins and signaling pathways.
Area of Science:
- Reproductive Toxicology
- Environmental Health
- Animal Science
Background:
- Melamine (MA) is a known reproductive toxicant, but the underlying mechanisms are not fully understood.
- The blood-testis barrier (BTB) is crucial for maintaining testicular function and protecting germ cells.
Purpose of the Study:
- To investigate the role of the blood-testis barrier (BTB) in melamine-induced reproductive toxicity in male piglets.
- To elucidate the molecular mechanisms by which MA affects BTB integrity and testicular function.
Main Methods:
- Male piglets were fed diets containing varying concentrations of MA (0-1000 mg/kg) for 10 weeks.
- Evaluated serum testosterone, testicular histopathology, BTB ultrastructure, BTB permeability, and expression of BTB junction proteins (ZO-1, occludin, N-cadherin, connexin-43).
- Assessed the involvement of the mitogen-activated protein kinase (MAPK) signaling pathway.
Main Results:
- MA exposure dose-dependently reduced serum testosterone levels and induced testicular and epididymal lesions.
- Significant damage to BTB structure and increased permeability were observed.
- MA decreased BTB junction protein levels and increased MAPK pathway activation (p-Erk, p-JNK, p-p38) in the testes.
Conclusions:
- Melamine exposure causes male reproductive toxicity in piglets by disrupting the integrity of the blood-testis barrier.
- MA-induced BTB disruption involves the downregulation of junctional proteins and activation of the MAPK signaling pathway.
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