Autologous mitochondrial microinjection; a strategy to improve the oocyte quality and subsequent reproductive outcome during aging

Abstract

Along with the decline in oocyte quality, numerous defects such as mitochondrial insufficiency and the increase of mutation and deletion have been reported in oocyte mitochondrial DNA (mtDNA) following aging. Any impairments in oocyte mitochondrial function have negative effects on the reproduction and pregnancy outcome. It has been stated that infertility problems caused by poor quality oocytes in women with in vitro fertilization (IVF) and repeated pregnancy failures are associated with aging and could be overcome by transferring large amounts of healthy mitochondria. Hence, researches on biology, disease, and the therapeutic use of mitochondria continue to introduce some clinical approaches such as autologous mitochondrial transfer techniques. Following mitochondrial transfer, the amount of ATP required for aged-oocyte during fertilization, blastocyst formation, and subsequent embryonic development could be an alternative modality. These modulations improve the pregnancy outcome in women of high reproductive aging as well. In addition to overview the clinical studies using mitochondrial microinjection, this study provides a framework for future approaches to develop effective treatments and preventions of congenital transmission of mitochondrial DNA mutations/diseases to offspring. Mitochondrial transfer from ovarian cells and healthy oocytes could lead to improved fertility outcome in low-quality oocytes. The modulation of mitochondrial bioactivity seems to regulate basal metabolism inside target oocytes and thereby potentiate physiological activity of these cells while overcoming age-related infertility in female germ cells.

Listening to mother: Long‐term maternal effects in mammalian development

“…Understanding the large impact of abnormal mitochondrial function on oocyte and embryo development has also led to new research looking at the effects of mitochondria replacement therapy. The thought behind these techniques, which can include pronuclear transfer, spindle transfer, ooplasm transfer, or mitochondrial microinjection, is that the mutant or defective mitochondria can be replaced or augmented with healthy donor mitochondria (Mobarak et al, 2019). However, these techniques are subject to both ethical and safety concerns (Adashi & Cohen, 2018).…”

“…In addition, mouse studies yielded progeny from mitochondria replacement procedures designed to overcome mitochondrial genetic defects (Adashi & Cohen, 2018; Sato et al, 2005). These methods generally had low mtDNA carryover, but heteroplasmy can be seen in progeny (Mobarak et al, 2019). However, studies to date from mitochondrial microinjection indicate that benefits may be limited in some contexts and may be affected by the cellular source of the mitochondria (Igarashi et al, 2016; Mobarak et al, 2019).…”

“…These methods generally had low mtDNA carryover, but heteroplasmy can be seen in progeny (Mobarak et al, 2019). However, studies to date from mitochondrial microinjection indicate that benefits may be limited in some contexts and may be affected by the cellular source of the mitochondria (Igarashi et al, 2016; Mobarak et al, 2019). The possible transgenerational effects of any heteroplasmy that would result from these methods have not been well studied.…”

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

“…Mitochondria are a major factor in the oocyte quality and are vital in the supply of sufficient ATP, but these may be directly affected during ovarian aging [1,11]. Although mitochondria have been hypothesized to be involved in energy metabolism, calcium homeostasis, growth and apoptosis [12,24,25], they have also been indicated to be the main source of intracellular ROS production [26,27]. Previous studies have reported that as age increases, the oocyte mass decreases, and mitochondrial dysfunction, oocyte mtDNA mutation, and deletion levels increase [12,28].…”

The Conundrum of Poor Ovarian Response: From Diagnosis to Treatment

“…AUGMENT described the Autologous Germline Mitochondrial Energy Transfer (AUGMENT). Their protocol involves isolation of mitochondria from the patient’s oogonial stem cells (OSCs), processed and injected into the patient’s own oocytes during ICSI [ 129 , 130 , 131 ]. The respective results failed to show an effectiveness through this novel technique, suggesting that it may be possible that the autologous mitochondrial transfer is suitable for a specific population that still remains to be identified.…”