Viral Infections and Male Infertility: A Comprehensive Review of the Role of Oxidative Stress

Abstract

Viral infections have been a part of human existence to date, though viruses have posed a huge threat with various outbreaks lately. These threats are associated with reproductive health challenges, especially male infertility. The prime focus of this review is to highlight the mechanisms associated with viral infection-induced male infertility/subfertility and identify new treatment strategies with the aim to preserve male fertility. The reviewed data showed that viral infections stimulate inflammatory responses, resulting in the release of proinflammatory cytokines, which induces oxidative stress. This oxido-inflammatory cycle could continue in a vicious cycle and threaten male fertility. Existing data from human and experimental studies show that viral infection-induced oxido-inflammatory response results in testicular damage, atrophy of the seminiferous tubules and Sertoli cells, and reduced Leydig cell mass. This is accompanied by reduced circulatory testosterone, impaired spermatogenesis, reduced sperm motility, lipid peroxidation, DNA fragmentation and apoptosis of the sperm cells. Based on the available pieces of evidence, antioxidant therapy, in vivo and in vitro, may be beneficial and protects against the potential risk of male infertility from viral infection. It is, however recommended that more clinical studies be conducted to demonstrate the possible protective roles of antioxidants used as adjuvant therapy in viral infections, and in the in vitro treatment of semen samples for those utilizing semen washing and artificial reproductive techniques.

Keywords: antiviral; apoptosis; infertility; inflammation; oxidative stress; retroviral; virus.

Figure 1

Enhanced generation of reactive oxygen species (ROS) could be a cause or consequence of inflammation; both of which can be triggered by viral infection and results in apoptosis.

Figure 2

Viruses upregulate the release of proinflammatory cytokines (IL-1, IL-6, and TNF-α), which enhance ROS release. In response, ROS promote cytokine release. This leads to a vicious cycle. ROS attack the polyunsaturated fatty acids of the plasma membrane, resulting in lipid peroxidation. They also trigger DNA fragmentation and apoptosis of the testes and sperm cells. In addition, the cytokines upregulate TNFR1, IL-6R, FAS, TLR-2, and TLR-4, resulting in reduced sperm motility and steroidogenesis.