Editorial: Oxidative stress and male fertility

Abstract

include reduced glutathione (GSH) and vitamins such as vitamin C and vitamin E (Irato and Santovito, 2021). On the flip side, the sources of ROS include endogenous (immature sperm, leukocytes, and varicocele), and exogenous such as environmental toxicants (heavy metals, air pollution, pesticides, and radiation), lifestyle (stress, alcohol intake, smoking of cigarette and other substance of abuse, fatty diet, and substance abuse), infections (urinary tract infections), testicular diseases (torsion/detorsion, cancer, cryptorchidism), chronic diseases (obesity, diabetes, and hypertension), and some medications (Baskaran et al., 2020;Adegbola et al., 2024;Akhigbe et al., 2024c;Akhigbe et al., 2024d;Akhigbe et al., 2025). Usually, these antioxidants mob off the generated free radicals, but sometimes, as seen in pathological conditions, the buffering capacity of the antioxidant system is overwhelmed, leading to ROS accumulation and oxidative stress.Although ROS (at optimal levels) play significant roles in several physiological, they also induce pathological processes when they are accumulated beyond their physiological levels. ROS act as physiological signaling molecule that is essential for the activation of steroidogenic pathway.Mitochondrial ROS mediate the phosphorylation of extracellualar signal-regulated kinase (ERK)1/2 and c-AMP-induced activation of Ras, which are critical components of Leydig cell proliferation and survival (Tai and Ascoli, 2011). ROS also promote sperm maturation by facilitating sperm DNA compaction and flagellar modifications (Baskaran et al., 2020). In addition to ERK1/2, ROS also promote the phosphorylation of JNK and p38 (MAPK families) in GSHdepleted cells (Chen et al., 2010). Furthermore, ROS regulate sperm capacitation, hyperactivation, acrosome reaction, and membrane fusion between the spermatozoa and the oocyte via the basification of intracellular pH, activation of cAMP-dependent signaling, removal of cholesterol from sperm membrane, and protein phosphorylation at serine, threonine, and tyrosine residues by cAMP-dependent kinases (Aitken, 2017). In sperm-oocyte fusion, ROS activate kinases, such as PKC, and inactivate phosphatases, leading to higher enzymatic PLA2 activity that in turn breaks down fatty acids in the membrane of the sperm cells, thus increasing the fluidity of the plasma membrane (Baskaran et al., 2020); a key process in fertilization. On the other hand, at pathological levels, ROS induces lipid peroxidation, resulting in membrane damage and mitochondrial dysfunction of the male reproductive organs/cells (Balló et al., 2023). ROS also trigger protein oxidation and sperm DNA damage by altering the protein structure and function, and promoting sperm DNA fragmentation respectively (Adeogun et al., 2024;Akhigbe et al., 2024b). ROS also induce mitochondrial and death receptor signaling, leading to apoptosis of the germ cells and other reproductive organs/cells (Besong and Akhigbe, 2024;Besong et al., 2024) [2001][2002][2003][2004] showed that red cell distribution width to albumin ratio was independently associated with ED risk, exhibiting a J-shaped relationship. This Collection does not only provide the link between oxidative stress and male fertility, it offers potential diagnostic and therapeutic strategies that are useful in the management of male infertility.

Topics & Concepts