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Published on: February 6, 2018
Methamphetamine induces apoptosis in seminiferous tubules in male mice testis
Yoshiko Yamamoto1, Keiichi Yamamoto, Tamaki Hayase
1Department of Legal Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Abstract:
We investigated whether methamphetamine (MAMP) induces apoptosis in seminiferous tubules in 10-week-old male ICR mice. Methamphetamine was dissolved in saline and injected ip at four doses (1, 5, 10, and 15 mg/kg). TUNEL-positive cells were detected in the seminiferous tubules in animals 24 h after a single treatment with 5, 10, or 15 mg/kg MAMP. The percentage of seminiferous tubules containing more than three TUNEL-positive cells (apoptotic tubules) was considered a reliable indicator for apoptotic changes. After a single treatment with 10 mg/kg MAMP, the percentage of apoptotic tubules increased with time, and it became significant at 24 h, at which time vacuolar changes in spermatogonia also peaked. Although the percentage of apoptotic tubules increased dose dependently from 5 to 15 mg/kg MAMP, the DNA ladder was detected in the testis of 15 mg/kg MAMP-treated mice. Thus, we have demonstrated that MAMP induces apoptosis in seminiferous tubules in male mice testis.
Insights
Methamphetamine (MAMP) causes cell death (apoptosis) in the reproductive organs of male mice. This study shows MAMP damages seminiferous tubules, impacting male fertility.
Area of Science:
- Reproductive Toxicology
- Cell Biology
- Pharmacology
Background:
- Methamphetamine (MAMP) is a potent psychostimulant with known systemic toxicity.
- Evidence suggests MAMP may negatively impact male reproductive health, but specific mechanisms are not fully elucidated.
- Apoptosis, or programmed cell death, is a critical process in spermatogenesis.
Purpose of the Study:
- To investigate the potential of methamphetamine (MAMP) to induce apoptosis in the seminiferous tubules of male mice.
- To determine the dose-response and time-course of MAMP-induced apoptotic changes in testicular tissue.
- To assess the impact of MAMP on spermatogonia and overall testicular integrity.
Main Methods:
- Male ICR mice (10 weeks old) were administered single intraperitoneal injections of MAMP at varying doses (1, 5, 10, 15 mg/kg) or saline.
- TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay was performed on testicular tissue to detect apoptotic cells.
- Histological examination assessed vacuolar changes in spermatogonia and quantified apoptotic tubules.
- DNA laddering assay was used to confirm DNA fragmentation indicative of apoptosis.
Main Results:
- MAMP treatment (≥5 mg/kg) induced a significant increase in TUNEL-positive cells within seminiferous tubules 24 hours post-injection.
- The percentage of apoptotic tubules showed a dose-dependent increase from 5 to 15 mg/kg MAMP.
- Apoptotic changes peaked at 24 hours, coinciding with observed vacuolar degeneration in spermatogonia.
- DNA laddering, a hallmark of apoptosis, was detected in testes of mice treated with the highest MAMP dose (15 mg/kg).
Conclusions:
- Methamphetamine (MAMP) demonstrably induces apoptosis in the seminiferous tubules of male mice.
- The observed apoptosis and spermatogonial damage suggest MAMP exposure can compromise testicular function and potentially male fertility.
- These findings highlight the reproductive toxicity of MAMP and warrant further investigation into its long-term effects on male reproductive health.
