The role of mitochondrial activity in female fertility and assisted reproductive technologies: overview and current insights

Abstract

Mitochondria have been implicated as key factors regulating female reproductive processes. Notable progress has been made in determining the role of mitochondria with respect to oocyte maturation, fertilization and early embryo development. In addition, mitochondrial function and dysfunction has been the subject of various studies in ovarian ageing and metabolic stress models. However, the overall mitochondrial impact on female fertility is yet to be uncovered. The mitochondrial DNA content of granulosa, cumulus and trophectoderm cells is being explored as a biomarker of oocyte quality and embryo viability. As growing evidence suggests that embryo potential could be related to the ability of oocyte mitochondria to generate energy, efforts have been made to investigate the possibility of improving mitochondrial capacity in women with poor outcomes after treatment with assistedreproductive technologies. Thus far, therapeutic attempts have focused mainly on using nutrients to restore mitochondrial function and transferring mitochondria from autologous germline precursor cells. Moreover, new perspectives on optimizing infertility treatments have arisen with modern mitochondrial replacement therapies, which are being applied in women with mitochondrial disease-causing mutations. This review explores aspects of the distinctive contribution of mitochondria to reproductive processes and discusses current and emerging clinical implications.

Updating the markers for oocyte quality evaluation: intracellular temperature as a new index

“…With aging, mtDNA deficiency of luteinizing granulosa cells and cumulus cells increases, which leads to a decrease in pregnancy rate . These findings corroborate the understanding that mitochondrial function of granulosa and cumulus cells directly influences embryonic development, as well as the maturation and fertilization of oocytes …”

“…66,67 These findings corroborate the understanding that mitochondrial function of granulosa and cumulus cells directly influences embryonic development, as well as the maturation and fertilization of oocytes. 68 Various mitochondrial anomalies have been linked to the agerelated deterioration of oocyte quality, and at least some of these may be reflective of the changes in specific mitochondrial subpopulations. 69 The most prominent of these defects are atypical mitochondrial localization and aggregation, reduced mtDNA content, reduced membrane potential (consequently, bioenergetic capacity), increased OS, and increased frequency of mtDNA mutations and deletions.…”

Combining Bioinformatics and Experiments to Identify CREB1 as a Key Regulator in Senescent Granulosa Cells

“…Previous studies have reported that as age increases, the oocyte mass decreases, and mitochondrial dysfunction, oocyte mtDNA mutation, and deletion levels increase [12,28]. Studies have also shown that the fertilization capacity and subsequent embryo growth potential of oocytes is directly proportional to the mtDNA content of older women, which is closely related to the ATP production in developing embryos [29]. Owing to the higher energy requirements of the developing embryos, oocyte maturation, division, preimplantation, and embryogenesis, a reduced glycolysis and preservation of the mtDNA function, prior to the oocyte blastocyst stage, provides the main source of ATP [30][31][32].…”

Early Life Oxidative Stress and Long-Lasting Cardiovascular Effects on Offspring Conceived by Assisted Reproductive Technologies: A Review

“…Specifically, during the maternal ageing process, significantly increased OS occurs in the ovarian and follicular environment, causing impaired oocyte quality and compromised oocyte meiosis [ 71 ]. Similar to men, unfavourable lifestyles and diets, adverse environmental and occupational exposures, and special treatments can also contribute to excessive OS in women [ 52 , 70 , 72 , 73 , 74 , 75 , 76 , 77 , 78 ] (as shown in Figure 2 ). Different from men, women exert OS on the offspring, not only through the fertilised oocytes, but also through the uterine environment throughout the whole pregnancy.…”