Cytotoxicity of methamphetamine exposure on Sertoli cells: a pilot study with implications for male infertility

Methamphetamine (Meth), a psychoactive drug, has been shown to reduce testicular weight and decrease sperm count, indicating its potential role in contributing to male infertility. We therefore assessed Meth's effects (0.1-100 μM) on TM4 Sertoli cell viability, toxicity, and proliferation (trypan blue exclusion assay), mitochondrial activity (MA) (XTT assay), while transepithelial electrical resistance (TEER) was used to examine monolayer permeability. The acute study (only 24-hour Meth exposure) mimics recreational users and the chronic study, the Meth addicts who require daily doses (24-96 hours). Acute Meth treatment had minimal impact on TM4 Sertoli cell viability and toxicity, while chronic exposure resulted in reduced cell viability and increased toxicity in a dose-related manner. Acute exposure suppressed cell division at 72 hours, while chronic exposure suppressed cell division at both 72 and 96 hours. Long-term suppression of MA was observed for both acute and chronic Meth exposure (20 µM and 100 µM). Both acute and chronic Meth exposure affected permeability across the blood-testis barrier (BTB), which persisted for up to 96 hours. Given the pivotal role of Sertoli cells in spermatogenesis, our findings provide a two-pronged mechanism for Meth-induced male infertility and indicate that short-term exposure may have long-term effects on the germinal epithelium.