Lonidamine transiently affects spermatogenesis in pubertal CD1 mice

Area of Science:

• Reproductive Biology
• Toxicology
• Developmental Biology

Background:

• Lonidamine (LND) is recognized for its antispermatogenic properties.
• Investigating LND's effects during the critical pubertal development phase is crucial for understanding its reproductive toxicity.

Purpose of the Study:

• To evaluate the impact of a single LND dose on spermatogenesis in pubertal mice.
• To determine the reversibility of LND-induced testicular effects and assess effects on sperm chromatin.

Main Methods:

• Pubertal male CD1 mice were administered a single oral dose of LND (100 mg/kg).
• Testicular assessments, including sperm counts, cell type distribution, and morphology, were performed at various time points post-dosing.
• Sperm chromatin structure assay was conducted on epididymal sperm from mature mice.

Main Results:

• Acute LND exposure led to significant testicular effects 48 hours post-dosing, including a ~50% reduction in sperm head concentration.
• Alterations in spermatogenic cell populations and Sertoli cell morphology were observed.
• Testicular effects and cell alterations were reversible by adulthood (PND74 and PND123).
• No adverse effects on sperm chromatin structure were detected in mature mice.

Conclusions:

• Lonidamine induces transient, dose-dependent disruptions in pubertal spermatogenesis.
• The observed testicular damage is reversible and does not affect sperm chromatin integrity in adulthood.
• LND's impact on spermatogenesis is temporary, highlighting the importance of developmental timing in assessing reproductive toxicants.