Mitochondria and reproduction: possibilities for testing and treatment

Mitochondria, known as the energy factories in all cells, are key regulators of multiple vital cellular processes and affect all aspects of mammalian reproduction, being essential for oocyte maturation, fertilization and embryonic development. Mitochondrial dysfunction is consequently implicated in disease as well as age-related infertility. Since mitochondria are inherited exclusively from the mother, the female gamete is central to reproductive outcome and therapeutic interventions, such as mitochondrial replacement therapy (MRT), and development of new diagnostic tools. The primary purpose of MRT is to improve oocyte quality, embryogenesis and fetal development by correcting the imbalance between mutant and wild-type mitochondrial DNA (mtDNA) in the oocyte or zygote, either by replacing mutant mtDNA or supplementing with wild-type counterparts from heterologous or autologous sources. However, the efficacy and safety of these new technologies have not yet been tested in clinical trials, and various concerns exist. Nonetheless, the perspectives for such procedures are intriguing and include two distinct patient populations that could potentially benefit from the clinical implementation of MRT; 1) patients with mtDNA-disease transmission risk; 2) patients undergoing IVF with recurrent poor embryo outcomes due to advanced maternal age. In this review, we outline the intrinsic roles of mitochondria during oogenesis and early embryogenesis in relation to disease and infertility, and discuss the progress in MRT with the developments in reproductive technologies and the related concerns. In addition, we assess the use of mtDNA as a potential biomarker for embryo viability in assisted reproduction.