Beyond the Powerhouse – Unveiling Hidden Influence of Mitochondria on Reproductive Health and Fertility

Mitochondria, recognised mainly for their role in adenosine triphosphate (ATP) production, are now understood to be pivotal regulators of reproductive function, extending their influence to gametogenesis, fertilisation, and early embryonic development. In males, mitochondrial dysfunction and excessive reactive oxygen species (ROS) generation compromise sperm motility, deoxyribonucleic acid (DNA) integrity, and fertilisation potential, contributing to infertility. Similarly, in females, proper mitochondrial activity is essential for oocyte maturation and embryonic viability, with mitochondrial DNA (mtDNA) abnormalities increasingly associated with ovarian ageing and diminished fertility. Emerging evidence also highlights the role of mitochondrial epigenetics, such as mtDNA methylation, non-coding ribonucleic acid (RNA) regulation, and retrograde signalling, in modulating reproductive outcomes. Disruptions to these pathways from ageing, metabolic disorders, environmental stressors, or assisted reproductive technologies (ART) can impair fertility in both sexes. Promising therapeutic strategies, including mitochondrial transfer, antioxidant supplementation, and modulation of mitochondrial dynamics, are still under investigation. A deeper understanding of mitochondrial function and its epigenetic interactions offers novel avenues for the diagnosis and treatment of infertility.