Fig. 2
The impact of human papillomavirus (HPV) infection on the male reproductive system and sperm quality. HPV infection in the male genital tract (MGT) is associated with increased viral load in the testis and epididymis, leading to an elevated risk of penile and testicular cancer, and reduced fertility. It also suggests potential co-infections with pathogens such as Ureaplasma, Urealyticum, Nontuberculous epididymitis, and HIV, which may exacerbate inflammation and oxidative stress (OS) in the reproductive tract and elevated risks of infertility. HPV DNA is detectable in all components of semen, including sperm cells, somatic cells, and seminal plasma. The infection in semen induces inflammation, recruiting immune cells and triggering the production of pro-inflammatory cytokines such as IL-1, IL-6, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ), which collectively contribute to reactive oxygen species (ROS) generation and OS. The resulting OS leads to increased DNA fragmentation, elevated pH levels, and abnormal sperm morphology. Furthermore, it negatively impacts hormonal and seminal parameters, including reduced testosterone levels, decreased semen volume, impaired sperm motility and viability, and lower total sperm count and concentration. In sperm cells, the interaction of HPV proteins, such as HPV-E2, with mitochondrial membrane proteins, leading to mitochondrial ROS release and OS. Co-expression of E1 and E2 proteins further exacerbates ROS production, increases DNA damage markers like γH2 AX, while decreasing glutathione (GSH) levels and superoxide dismutase 2 (SOD2) activity. Additionally, the disruption of AQP8 by the viral L1 protein impairs water and hydrogen peroxide (H2O2) transport and detoxification processes, contributing to sperm stress and functional impairment. HPV infection also leads to the production of ASA. HPV-infected sperm cells act as carriers for HPV antigens, initiating or boosting a humoral immune response in HPV-naïve or HPV-experienced women, respectively. This immune response can result in the antibody-mediated elimination of both HPV-infected and uninfected sperm cells, further compromising fertility. The interplay between ASA and anti-HPV antibodies, and their contribution to infertility, remains an area for further investigation