Abstract

Significance: In recent decades, male fertility has been severely reduced worldwide. The causes underlying this decline are multifactorial, and include, among others, genetic alterations, changes in the microbiome, and the impact of environmental pollutants. Such factors can dysregulate the physiological levels of reactive species of oxygen (ROS) and nitrogen (RNS) in the patient, generating oxidative and nitrosative stress that impairs fertility.Recent Advances: Recent studies have delved into other factors involved in the dysregulation of ROS and RNS levels, such as diet, obesity, persistent infections, environmental pollutants, and gut microbiota, thus leading to new strategies to solve male fertility problems, such as consuming prebiotics to regulate gut flora or treating psychological conditions.Critical Issues: The pathways where ROS or RNS may be involved as modulators are still under investigation. Moreover, the extent to which treatments can rescue male infertility as well as whether they may have side effects remains, in most cases, to be elucidated. For example, it is known that prescription of antioxidants to treat nitrosative stress can alter sperm chromatin condensation, which makes DNA more exposed to ROS and RNS, and may thus affect fertilization and early embryo development.Future Directions: The involvement of extracellular vesicles, which might play a crucial role in cell communication during spermatogenesis and epididymal maturation, and the relevance of other factors such as sperm epigenetic signatures should be envisaged in the future.