TESTICULAR TOLL WITH VIRAL INTRUSION: MOLECULAR INSIGHTS INTO THE IMPACT OF CHRONIC HIV INFECTION ON MALE FERTILITY
HIV infection remains a major global health concern, compromising immune function and increasing susceptibility to opportunistic infections. Over the past two decades, fertility desire among people living with HIV has remained low due to poor health, fear of transmission, and restrictive reproductive policies. In men, particularly during those in advanced stages of infection, HIV has been associated with profound alterations in semen quality, including reduced ejaculate volume, impaired sperm motility, abnormal morphology, and increased incidence of sperm aneuploidy factors that collectively contribute to male infertility. This study explored the molecular mechanisms of HIV-associated male infertility using a preclinical HIV transgenic (Tg) rat model. RT-PCR revealed marked downregulation of CatSper 1-4 channel gene expressions, along with dysregulation of mitochondrial and inflammatory gene networks in the testes of Tg animals. Histopathological examination further demonstrated structural disruptions within the seminiferous tubules of Tg rats. Functional assessments using computer-assisted semen analysis (CASA) and nuclear morphology analysis confirmed reduced motility and abnormal sperm morphology in Tg rats. Complementary transcriptomic sequencing identified novel gene signatures and disrupted pathways associated with testicular dysfunction in Tg rats. Collectively, our findings show that HIV-1 infection impairs sperm production and function by disrupting ion channel regulation and perturbing broader molecular pathways, ultimately contributing to male infertility. Collectively, this study provides clinically relevant insights into reproductive complications in HIV-infected individuals and may inform future therapeutic strategies.