The Dual Role of Oxidants in Male (In)fertility: Every ROSe Has a Thorn

Abstract

The role of oxidative stress (OS) in male infertility as a primary etiology and/or concomitant cause in other situations, such as inflammation, varicocele and gonadotoxin effects, is well documented. While reactive oxygen species (ROS) are implicated in many important roles, from spermatogenesis to fertilization, epigenetic mechanisms which are transmissible to offspring have also recently been described. The present review is focused on the dual aspects of ROS, which are regulated by a delicate equilibrium with antioxidants due to the special frailty of spermatozoa, in continuum from physiological condition to OS. When the ROS production is excessive, OS ensues and is amplified by a chain of events leading to damage of lipids, proteins and DNA, ultimately causing infertility and/or precocious pregnancy termination. After a description of positive ROS actions and of vulnerability of spermatozoa due to specific maturative and structural characteristics, we linger on the total antioxidant capacity (TAC) of seminal plasma, which is a measure of non-enzymatic non-proteic antioxidants, due to its importance as a biomarker of the redox status of semen; the therapeutic implications of these mechanism play a key role in the personalized approach to male infertility.

Keywords: antioxidants; capacitation; male infertility; oxidative stress; spermatozoa.

Figure 1

Left panel: redox homeostasis with positive effects of ROS; central panel: oxidative stress situation due to increased ROS production and consequential oxidative damages; right panel: reductive stress situation with low ROS levels and consequential detrimental effects.

Figure 2

Infographic summary of main characteristics of spermatozoa associated with their vulnerability toward ROS attack.

Figure 3

The components of “total” antioxidant capacity of seminal plasma, i.e., “Fast” (low-molecular-weight chain-breaking antioxidants) and “Slow” (antioxidant enzymes, e.g., SOD). In ordinate, “I_A” represents the absorbance at 734 nm; in abscissa, “t” represents the time expressed in seconds. ABTS radical species appear after the initial period (latency phase) with the enrollment of “Fast” component, then gradually increase until a plateau related to the “Slow” component.