Mitochondrial activity and redox status in oocytes from old mice: The interplay between maternal and postovulatory aging

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Maternal aging has been reported to reduce oocyte quality and, in turn, lower the developmental potential of the resulting embryos. Here, we show that maternally aged oocytes display two strikingly different phenotypes: some have normal morphology, whereas others have significantly shrunk cytoplasm. The latter phenotype usually prevails in aged females. Our objective was to characterize both types of maternally aged oocytes and investigate the origins of this diversity. Importantly, our experiments indicate that shrunk maternally aged oocytes are severely compromised in terms of mitochondrial functionality as compared to their young or morphologically normal maternally aged counterparts: they display significantly decreased mitochondrial activity and lower amounts of ROS. In contrast, morphologically normal maternally aged oocytes had the same mitochondrial activity as young ones, while their ROS levels were higher. Surprisingly, the shrunk phenotype was completely absent in maternally aged oocytes that matured in vitro, suggesting that it is not caused inherently by maternal aging, but may be related to other factors, like postovulatory aging. Indeed, an additional culture of in vitro matured young and old oocytes (i.e., in vitro postovulatory aging) significantly decreased their mitochondrial activity and led to cytoplasm shrinkage. In vivo postovulatory aging had a similar effect on oocytes from both young and old females. Finally, we examined the developmental potential of oocytes obtained from aged females. Shrunk (i.e., most likely postovulatory aged) oocytes failed to become fertilized, whereas morphologically normal ones (i.e., most likely not subjected to postovulatory aging) underwent fertilization and subsequent cleavage divisions, although they achieved the 2-cell stage less frequently than morphologically normal oocytes from young females. Importantly, the quality of blastocysts as well as the live birth rate for morphologically normal oocytes from old and young females were similar. In summary, our data clearly indicate that two pools of oocytes present in oviducts of aged females differ significantly in their quality and developmental potential and that the more severely affected phenotype results most likely from a synergistic action of maternal and postovulatory aging.