The role of sperm mitochondria in occurrence and development of male infertility

Abstract

The aim of this review was to analyze current data on the role of sperm mitochondria in the occurrence and development of reproductive pathologies. Mitochondria play a major role in the sperm metabolism due to their participation in the synthesis of high-energy phosphates; maintenance of redox potential; regulation of the sperm proliferation rate, differentiation, apoptosis, and mitophagy; generation of reactive oxygen species; implementation of intracellular signaling, and other processes that ensure flagella motility, capacitation, acrosomal reaction, oocyte activation, and gamete fusion. In most cases, changes in these functions are associated with subfertility and/or infertility. A close relationship between the mitochondrial genome, proteome, metabolome, and sperm fertility has also been demonstrated. The key mitochondrial proteins (ATP synthase, adenylate translocase, adenylate kinase 1, isocitrate dehydrogenase 3β, aconitate hydratase, fumarate hydratase, pyruvate dehydrogenase complex, sirtuins, peroxiredoxins, etc.) involved in the reproductive process were identified. Correlations were found between the aberrant gene expression of these proteins and the deterioration of qualitative and quantitative characteristics of the ejaculate. The obligate role in sperm metabolism of mitochondrial energy substrates, such as lactate and long-chain fatty acids, has been proved. At the same time, the high plasticity of mitochondria, which relatively easily modulate their localization, shape, and metabolic activity, makes it difficult to interpret unambiguously the currently available body of facts on their functions. Deciphering the molecular genetic mechanisms of mitochondrial structural disorders and dysfunction may become a basis for development of effective diagnostic methods and targeted therapy for male infertility.