Association of Zidovudine or Nevirapine Treatment with Sperm Abnormalities Across Two Generations of Albino Mice

Background and Objective: The long-term use of antiretroviral drugs has raised concerns beyond improvements in the quality of life of people living with HIV (PLWH), including reproductive challenges among PLWH. Many PLWH desire to have children, but human immunodeficiency virus (HIV) infection and/or antiretroviral therapy may hinder this possibility. This study sought to evaluate the influence of zidovudine [ZDV] or nevirapine [NVP] on the sperm and testes of albino mice across two generations. Methods: ZDV (10, 100, and 250 mg/kg) and NVP (5, 50, and 150 mg/kg) were administered through gavage throughout one spermatogenic cycle to the parental generation of mice. Testicular weight, sperm counts, sperm head anomalies, and sperm deoxyribonucleic acid (DNA) quantity were determined for the treatment and control groups. Hemocytometry and microscopy were used to determine sperm counts and sperm head anomalies. Fluorometric evaluations of picogreen-labeled DNA were used to determine the quantity of sperm DNA. Results: Among the parental generation, sperm counts were significantly reduced among all treatment groups, but changes in sperm DNA quantity were not significantly different. Among the F1 groups, there were significant reductions in testicular weight, sperm counts, and sperm DNA quantity. Changes in sperm head morphology appeared transient among the parental generation and were not significantly different among the F1 generation. Conclusion and Implications for Translation: Administration of ZDV or NVP to mice resulted in significant oligospermia in both the parental and F1 groups. Across both generations, ZDV affected sperm DNA quantity, sperm counts, and sperm morphology, while NVP mainly impacted sperm DNA quantity. The transgenerational effect observed calls for monitoring among HIV-positive adolescents on lifelong treatment for possible adverse effects on male reproductive health.