High‐Resolution Imaging Reveals Mitochondrial Protein Imbalance in Sperm of Oligoasthenospermic Men

Male infertility accounts for nearly half of global infertility cases and is often linked to poor sperm quality, such as oligospermia, asthenospermia, and teratospermia. Although the exact mechanisms remain unclear, mitochondria, which are critical for ATP production and reactive oxygen species generation during fertilization, are increasingly recognized as key players in male infertility but remain underexplored. ATP synthesis relies on respiratory chain complexes that establish a proton gradient across the inner mitochondrial membrane, powering the F0F1-ATP synthase. Proper stoichiometry of these complexes, encoded by both nuclear and mitochondrial DNA, is essential for efficient energy production. However, no previous studies have directly correlated mitochondrial protein expression with sperm quality. Due to the small size and helical structure of sperm mitochondria, imaging them is challenging, yet crucial for understanding sperm function. This study investigates the role of mitochondrial oxidative phosphorylation proteins in sperm quality using single-cell immunolabeling and high-resolution microscopy. It compares spermatozoa from oligoasthenospermic (OA) patients to normospermic controls. OA sperm show increased levels of mitochondrial genome encoded cytochrome c oxidase subunit 1 and significantly reduced F0F1-ATP synthase subunits. This imbalance may contribute to mitochondrial dysfunction and underscores the need for deeper exploration of the pathophysiological mechanisms involved, which could affect sperm function and fertility. These initial results suggest a potential pathway toward the identification of novel biomarkers of male infertility.