Mitochondrial Regulation of Spermatozoa Function: Metabolism, Oxidative Stress and Therapeutic Insights

Abstract

Mitochondria are central to energy production and redox regulation in spermatozoa, supporting key functions such as progressive motility, capacitation, and the acrosome reaction. These processes are essential for successful fertilization and embryo development. However, species-specific differences exist in the reliance on oxidative phosphorylation versus glycolysis. Mitochondria also generate reactive oxygen species, which at physiological levels aid in sperm function but can cause oxidative stress and damage when overproduced. Mitochondrial dysfunction and excessive ROS can impair membrane potential, induce apoptosis, and damage nuclear and mitochondrial DNA, ultimately compromising sperm quality. Sperm mitochondrial DNA is highly susceptible to mutations and deletions, contributing to reduced motility and fertility. Targeted antioxidant strategies have emerged as promising therapeutic interventions to mitigate oxidative damage. This article provides a comprehensive overview of mitochondrial regulation in spermatozoa, the consequences of redox imbalance, and the potential of mitochondria-targeted antioxidants to improve sperm function and male fertility outcomes. The paper aims to deepen our understanding of mitochondrial roles in sperm physiology and contribute to the advancement of strategies for addressing male infertility.

Keywords: antioxidant; energy metabolism; mitochondria; mtDNA; reactive oxygen species; spermatozoa.

Figure 1

Effects of mitochondrial ROS on spermatozoa. Note: Mitochondria are the major source of ROS in sperm. Excessive ROS can damage sperm MMP (Δψ), as well as sperm nuclear DNA and mtDNA damage. At the same time, ROS also plays an important role in sperm maturation, capacitation and acrosome reaction.