MITOCHONDRIAL DYSFUNCTION IN MALE SUB-FERTILITY: WHERE DO NUTRACEUTICALS STAND?

Vineet Malhotra, Ajit Saxena, Nayan Kumar Mohanty, Rajeev Sood, Rahul Reddy, P. B. Sivaraman, Anup Kumar Kundu, Vijay Kulkarni, T. P. Rajeev, D. Ramesh, Anish Desai and Sunaina Anand*

ABSTRACT

Mitochondria plays a crucial role in male fertility by contributing to energy synthesis, meiosis, spermatogenesis, sperm maturation, and capacitation. Mitochondrial dysfunctions, in particular mitochondrial DNA (mtDNA) mutation, generation of reactive oxygen species (ROS), and lowered antioxidant capacity are associated with male sub-fertility. Under physiological conditions, sperms produce basal level of ROS necessary for sperm function. However, increased production of ROS causes DNA fragmentation and peroxidative damage to sperm plasma membrane, inducing cell death and causing a decline in fertility. Antioxidants could be employed to control the oxidative damage caused by excessive ROS during spermatogenesis. Mitochondrial medicine was introduced into clinical practice based on pathologies caused by abnormal functioning of mitochondria. Since then, various strategies have been implemented to develop mitochondrial therapeutics, including use of vitamins, co-factors, and antioxidants. The major supplementary antioxidants approved to manage male sub-fertility are L-carnitine, CoQ10, vitamin C, vitamin E, and Lycopene, as well as micronutrients such as folate and zinc. Evidence suggest favourable effects of nutraceutical-based antioxidant supplementation, alone or in combination, on sperm parameters such as sperm concentration, motility, and morphology. In this direction, future studies designed to precisely measure dosage, type, and duration of mitochondria-targeted treatments will encourage widespread use in clinical practices.

Keywords: Mitochondria, antioxidants, spermatogenesis.