Mitochondrial DNA quantity Counteracts ROS damage in oocytes during female reproductive aging

We investigated the contentious role of mitochondrial reactive oxygen species (ROS) on mitochondrial DNA (mtDNA) quality and quantity in female reproductive aging. By conditionally knocking out the Sod2 gene in female mouse germline, we observed increased mitochondrial ROS and decreased oocyte quality, primarily due to impacts on OXPHOS complex II and mtDNA encoded mRNA levels. Interestingly, we found no increased mtDNA mutations, but alterations in mtDNA quantity, indicating the susceptibility of mtDNA to the mitochondrial ROS during reproductive aging. Notably, when we further decreased the basal level of mtDNA quantity by deactivating the mtSSB protein in Sod2 conditional knockout females, we observed an exacerbation of reproductive aging effects. This highlights the crucial role of mtDNA quantity in mitigating the impact of oxidative stress on fertility. Overall design: To examine the molecular alterations in oocytes caused by elevated levels of mitochondrial matrix ROS, we employed the Smart seq2 method to study the transcriptomic alterations in mature oocytes from approximately six-month-old females between L/L cre mice and L/L mice.