Poor embryo development in post-ovulatory in vivo-aged mouse oocytes is associated with mitochondrial dysfunction, but mitochondrial transfer from somatic cells is not sufficient for rejuvenation.

STUDY QUESTION

Does in vivo aging of mouse oocytes affect mitochondrial function?

SUMMARY ANSWER

Mitochondrial function was impaired in post-ovulatory in vivo-aged mouse oocytes and microinjection of somatic cell mitochondria did not rescue poor fertilization and embryonic development rates.

WHAT IS KNOWN ALREADY

The mechanisms underlying the decline in oocyte quality associated with oocyte aging remain unknown, although studies have suggested that the decline is regulated by mitochondrial dysfunction. However, only a limited number of studies have provided direct evidence implicating mitochondrial dysfunction in oocyte quality during the aging of oocytes.

STUDY DESIGN, SIZE, DURATION: We used post-ovulatory, in vivo-aged mouse oocytes as a model for studying low-quality oocytes in oocyte aging.

PARTICIPANTS/MATERIALS, SETTING, METHOD: Superovulated oocytes released from the oviduct at 14 h and 20-24 h post-hCG injection were designated as 'fresh' and 'aged' oocytes, respectively. Membrane potentials and oxygen consumption in single oocytes were evaluated as measures of mitochondrial function in fresh and aged oocytes. Mitochondrial transcriptional factor A (TFAM) expression levels were examined by western blotting, and colocalization of mitochondria and TFAM was analyzed by measuring immunofluorescence in fresh and aged oocytes. IVF and blastocyst formation rates were calculated after oocyte microinjection with mitochondria derived from liver cells.

MAIN RESULTS AND THE ROLE OF CHANCE

The average mitochondrial membrane potential in fresh oocytes was significantly higher than that in aged oocytes (P < 0.05). The average oxygen consumption rate in aged oocytes was significantly lower than that in fresh oocytes (P < 0.05). Although total TFAM expression was unchanged, its colocalization with mitochondria decreased in aged oocytes. IVF and blastocyst formation rates for mitochondrion-injected aged oocytes were not significantly different from those for buffer-injected aged oocytes.

LARGE SCALE DATA

Not applicable.

LIMITATIONS, REASONS FOR CAUTION: A limitation of this study is that we did not examine the effects of microinjecting mitochondria from other somatic cell types into aged oocytes on their fertilization and embryonic development rates.

WIDER IMPLICATIONS OF THE FINDINGS

The results from the present study showed that poor embryonic development was associated with impairment of mitochondrial functions in in vivo-aged oocytes. However, the microinjection of mitochondria from liver cells did not improve the low fertilization and embryonic development rates of aged oocytes. It remains to be demonstrated whether oocyte quality can be rescued by the transfer of cytosolic factors or cellular organelles, such as the endoplasmic reticulum or mitochondria, from specific cell types.

STUDY FUNDING/COMPETING INTERESTS: This study was supported by Grants-in-Aid for General Science Research to Toshifumi Takahashi (No. 25462550) and Hideki Igarashi (No. 26462474). The funding source played no role in study design in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. The authors have no conflict of interest to disclose.