Oxidative Stress and Male Infertility: Evidence From a Research Perspective

Abstract

Male fertility potential can be influenced by a variety of conditions that frequently coincide. Spermatozoa are particularly susceptible to oxidative damage due to their limited antioxidant capacity and cell membrane rich in polyunsaturated fatty acids (PUFAs). The role of oxidative stress (OS) in the etiology of male infertility has been the primary focus of our Stellenbosch University Reproductive Research Group (SURRG) over the last 10 years. This review aims to provide a novel insight into the impact of OS on spermatozoa and male reproductive function by reviewing the OS-related findings from a wide variety of studies conducted in our laboratory, along with those emerging from other investigators. We will provide a concise overview of the production of reactive oxygen species (ROS) and the development of OS in the male reproductive tract along with the physiological and pathological effects thereof on male reproductive functions. Recent advances in methods and techniques used for the assessment of OS will also be highlighted. We will furthermore consider the current evidence regarding the association between OS and ejaculatory abstinence period, as well as the potential mechanisms involved in the pathophysiology of various systemic diseases such as obesity, insulin resistance, hypertension, and certain mental health disorders which have been shown to cause OS induced male infertility. Finally, special emphasis will be placed on the potential for transferring and incorporating research findings emanating from different experimental studies into clinical practice.

Keywords: diabetes mellitus; hypertension; male infertility; obesity; oxidative stress; semen analysis.

Figure 1

Role of reactive oxygen species (ROS) in sperm function. (A) Physiological role of ROS, (B) Pathological effect of ROS on sperm function.

Figure 2

Effect of short abstinence on sperm function. Decrease in the length of abstinence (short abstinence) leads to a reduction in ROS levels and an increased antioxidant level, which consequently reduces the rate of sperm membrane lipid peroxidation.

Figure 3

Hypertension and the development of oxidative stress. In the occurrence of hypertension, there is proliferation of the vascular smooth muscles and the narrowing of vascular lumen. The narrowing of the vascular lumen leads to increase in the generation of ROS, thus causing oxidative stress.

Figure 4

Obesity-induced oxidative stress and male infertility. Obesity-induced oxidative occurs because of (i) increase in metabolic reaction due to elevated glucose and lipids levels, (ii) increase in the level of stress hormones and proteins and (iii) alteration in genetic composition. The occurrence of oxidative stress leads to disrupted hypothalamo-pituitary gonadal axis, induction of apoptosis, increased sperm DNA fragmentation and alters cell cycle, which cumulatively result in male infertility.

Figure 5

Diabetes and impaired sperm function. Hyperglycaemia can increase the production of advanced glycation end products, thereafter causing imbalance in the ratio of ROS generation and its elimination by antioxidants, thereby resulting in the development of oxidative stress.