Reproductive aging is associated with decreased mitochondrial abundance and altered structure in murine oocytes

Abstract

To establish the phenotype of reproductive aging in our mouse model. To test the hypotheses that reproductive aging is associated with a decrease in mitochondrial abundance that could ultimately reflect dysfunction in oocytes. Breeding studies were performed in young and aged female virgin wild type C57BL6J mice to establish their reproductive phenotype by measuring time to conception, litter size, and live birth per dam. Individual oocytes were analyzed for mtDNA content. Transmission electron microscopy was used to study ultrastructure of mitochondria in oocytes. Old females were found to have significantly prolonged time to conception and fewer surviving pups in their litters. Oocytes from old mice had 2.7-fold less mtDNA compared to younger controls (p < 0.001; 95% CI 2.1-3.5). Decrease in mitochondrial organelle abundance in old animal's oocytes was confirmed with transmission electron microscopy. Distinct morphological changes were noted in mitochondria, suggesting altered mitochondrial biogenesis in the old animals' oocytes. Reproductive aging in mice is associated with reduced reproductive competence. Aging is associated with a significant decrease in number of mitochondria in oocytes. Our data support mitochondrial organelle loss and dysfunction in oocytes as a potential etiology for reproductive senescence.