Antioxidants and Male Fertility: from Molecular Studies to Clinical Evidence

Abstract

Spermatozoa are physiologically exposed to reactive oxygen species (ROS) that play a pivotal role on several sperm functions through activation of different intracellular mechanisms involved in physiological functions such as sperm capacitation associated-events. However, ROS overproduction depletes sperm antioxidant system, which leads to a condition of oxidative stress (OS). Subfertile and infertile men are known to present higher amount of ROS in the reproductive tract which causes sperm DNA damage and results in lower fertility and pregnancy rates. Thus, there is a growing number of couples seeking fertility treatment and assisted reproductive technologies (ART) due to OS-related problems in the male partner. Interestingly, although ART can be successfully used, it is also related with an increase in ROS production. This has led to a debate if antioxidants should be proposed as part of a fertility treatment in an attempt to decrease non-physiological elevated levels of ROS. However, the rationale behind oral antioxidants intake and positive effects on male reproduction outcome is only supported by few studies. In addition, it is unclear whether negative effects may arise from oral antioxidants intake. Although there are some contrasting reports, oral consumption of compounds with antioxidant activity appears to improve sperm parameters, such as motility and concentration, and decrease DNA damage, but there is not sufficient evidence that fertility rates and live birth really improve after antioxidants intake. Moreover, it depends on the type of antioxidants, treatment duration, and even the diagnostics of the man's fertility, among other factors. Literature also suggests that the main advantage of antioxidant therapy is to extend sperm preservation to be used during ART. Herein, we discuss ROS production and its relevance in male fertility and antioxidant therapy with focus on molecular mechanisms and clinical evidence.

Keywords: antioxidants therapy; assisted reproductive technologies; infertility; pregnancy; reproductive outcome; sperm ROS.

Figure 1

Potential stimuli that cause reactive oxygen species (ROS) production in spermatozoa.

Figure 2

Proposed model of the bivalent role of reactive oxygen species (ROS) in sperm. (i) High levels of ROS concentration induced by different factors such as assisted reproductive technologies (ART), diseases, medical treatment, life style, etc., overwhelming the sperm antioxidant system induce plasma membrane lipid peroxidation and DNA damage. (ii) Physiological ROS level produced mainly by mitochondria induce production of high levels of cAMP by an undetermined mechanism, activating the PKA pathway, and leading to tyrosine phosphorylation, a hallmark of sperm capacitation.

Figure 3

Haber–Weiss Reaction and Fenton reaction.