The role of mitochondrial dynamics in oocyte and early embryo development

Over the past decade, there has been a significant increase in our understanding of the profound impact mitochondrial dysfunction may have on human diseases. While primarily recognized for their crucial role in generating energy, mitochondria also play a critical role in controlling cellular processes (e.g., cell death), managing calcium levels, supporting the innate immune response, and synthesizing phospholipids [1], [2], [3], [4], [5]. The wide array of functions that mitochondria perform highlights their significance for all cell types. This is especially true for cells with a high energy-demand, such as skeletal and cardiac muscle cells, and neurons, which are particularly susceptible to problems arising from mitochondrial dysfunction [2]. In addition, multiple studies have shed light on the potential mechanisms underlying how mitochondrial dysfunction may be involved in disorders of the reproductive system.

In humans, the aging process triggers malfunction of the ovary, leading to a progressive decline in both the number of follicles and the quality of eggs. As a result, the rate of cumulative live birth per retrieval in women undergoing infertility treatment with assisted reproductive technologies (ART) decreases from 54.1% in women below the age of 35 to 9.3% in women above 40 years of age [6], [7]. While the reduced number of follicles is thought to stem from follicle atresia caused by programmed cell death (apoptosis), the primary reason for compromised egg quality is attributed to aneuploidy associated with meiotic errors [7]. In this context, the mitochondrion emerges as a crucial organelle due to its pivotal role in both apoptosis and energy generation. These functions have been found to be intricately linked to proper spindle assembly and the segregation of chromosomes [8], [9], [10], [11], [12].

In this review we aimed to summarize current knowledge regarding the role of mitochondrial dynamics in reproduction. Specifically, we will first discuss the basic functions associated with mitochondrial dynamics, including fusion, fission, and mitophagy, and how these processes are regulated within the context of reproduction. Next, we will review findings in animal models and human studies regarding the role of mitochondrial dynamics in oocyte and early embryo development. We will particularly focus on the possible ways in which mitochondrial findings may help inform novel therapeutic interventions aimed at improving fertility and reproductive health.

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