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Mitochondrial Transfer Partially Reverses Some Consequences of Oocyte Aging

This is a most interesting technology demonstration for anyone interested in the various aspects of mitochondrial contributions to aging: transferring mitochondria from fat-derived cells into germline cells in an older mouse can reverse some of the consequences of aging in the germline, specifically loss of fertility in females. Mitochondria are the power plants of the cell, primarily responsible for generating chemical energy store molecules, though they have many other roles in fundamental cellular activities as well. There are a couple of different aspects to mitochondrial dysfunction in aging, and the research here is probably relevant to the one unconnected to SENS rejuvenation research: the general malaise that affects mitochondria throughout the body, probably a reaction to rising levels of other molecular damage, that changes mitochondrial dynamics and reduces available energy for cellular operations. The research results noted here raise many questions regarding the mechanisms involved in different rates of decline of mitochondrial function throughout the body.

The fertility of women decreases with maternal aging, resulting from various kinds of reasons including decreased follicle number, altered reproductive endocrinology, increased reproductive tract defects, decreased embryo quality, and impaired oocyte quality. Among the possibilities, decreased oocyte quality with maternal aging is the main reason because oocyte donation from young women could rescue the low live birth rate in elder women. With maternal aging, both the nuclear maturation and cytoplasmic quality are affected, and oocyte aneuploidy arising from chromosome segregation error increases dramatically. The obvious change in ooplasm with maternal aging is mitochondrial dysfunction.

It is well known that mitochondria function in energy production and apoptosis in cells. As the most prominent cell organelles in oocytes, mitochondria play pivotal functions and determine the developmental competence of oocytes. With advanced maternal age in women, the most common aberrations in mitochondrial structure are mitochondrial swelling and cristae disruption. Mitochondria are the main source of ATP through oxidative phosphorylation in mammalian oocytes. It is reported that reduced ATP content and metabolic level could be detected in aged oocytes, which would affect oocyte quality and embyogenesis. Mitochondrial malfunction is highly related with defects in spindle organization, cell cycle progress and chromosome segregation in oocytes of aged women and mice. Mitochondrial dysfunction is a major contributing factor for negative outcomes in IVF in general, especially in women of advanced maternal age. The findings reminded the researchers that mitochondria supplement or replacement in oocytes might be a possible strategy for infertility treatment in elder women.

The mitochondria replacement by transfer of heterologous ooplasm, germinal vesicle, spindle, polar body, or pronuclei has been tested in animals and humans to improve developmental potential of aged defective oocytes or to prevent trans-generational mitochondrial disease transmission, but clinical translation of these techniques requires further validation for their efficacy and safety. Especially, the compatibility between donor and recipient mitochondrial DNA and mitochondrial heteroplasmy are still a concern. Transfer of autologous mitochondria from cumulus and granulosa cells were tested for oocyte quality rescue, but it is worth noting that cumulus and granulosa cells age similarly to oocytes. We supposed that autologous adipose tissue-derived stem cell (ADSCs) might be an ideal mitochondrial source for rescuing oocyte quality and fertility. In our study, we found that supplement of autologous ADSC mitochondria could improve oocyte quality, embryogenesis, and fertility in aged mice. We propose that autologous ADSC mitochondria supplement may be a promising strategy for fertility retrieval in women with advanced reproductive age.

Link: https://doi.org/10.18632/aging.101332

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