Role of Sperm-Hyaluronic Acid Binding in the Evaluation and Treatment of Subfertile Men with ROS-Affected Semen

Excessive levels of free radicals diminish the functional integrity of spermatozoa. Levels of reactive oxygen species (ROS) produced by spermatozoa were negatively correlated with the quality of sperm in the original semen. “Intrinsic,” “extrinsic,” and “iatrogenic” sources of ROS production were identified within semen: intrinsic sources of ROS in semen are morphologically abnormal and arrested-maturity spermatozoa and leukocytes. Poor sperm quality showing attributes of arrested sperm maturation is linked to increased ROS generation as a consequence of excess residual cytoplasm related to the arrest of cytoplasmic extrusion in terminal spermiogenesis. In the past 30 years, the Huszar lab has studied several key events of sperm maturation, including cytoplasmic extrusion and expression of the HspA2 chaperone protein. In experiments related to sperm function and fertilizing potential, it has been established that, simultaneously with cytoplasmic extrusion during terminal spermiogenesis, there is a remodeling of the plasma membrane that facilitates the formation of the zona pellucida and hyaluronic acid (HA)-binding sites. The studies with HA immobilized to glass slides or Petri dishes showed that sperm firmly bind to HA. However, not all sperm exhibited HA-binding ability. These data supported the hypothesis that the ability of sperm-HA binding is related to sperm cellular maturity. Although, recent literature on the efficacy with HA selection of human sperm reported a lack of efficacy but with the caution that is either inadequately powered or of low-quality, HA-mediated sperm ICSI selection may increase fertilization rates and paternal contribution of sperm to the embryo even if the man to be treated is affected by seminal ROS production. Indeed, well-designed new studies are needed to evaluate this aspect in terms of potential evaluation and treatment of subfertile men with ROS-affected semen utilizing HA.