Abstract
The mtDNA ‘mutator’ mouse, also called the ‘POLG’ mouse, is a well-characterized model frequently used for studies of progeroid aging. Harboring a mutation in the proofreading domain of the mitochondrial polymerase, polymerase-γ (Polg), POLG mice acquire mtDNA mutations at an accelerated rate. This results in premature mitochondrial dysfunction and a systemic aging phenotype. Previous work has demonstrated that the progeroid phenotype in POLG is attenuated following endurance exercise, the only reported intervention to extend health span and lifespan of these mice. Herein, oocyte quality was evaluated in sedentary and exercised POLG mice. In mice homozygous for the Polg mutation, litter size is dramatically reduced as compared to heterozygous Polg mice. Following ovarian hyper-stimulation, oocytes were retrieved until 9 months of age in exercised and sedentary groups, with no oocytes ovulated thereafter. Although ovulated oocyte numbers were not impacted by exercise, we did find a modest improvement in both the ovarian follicle reserve and in oocyte quality based on meiotic spindle assembly, chromosomal segregation and mitochondrial distribution at 7 months of age in exercised POLG mice as compared to sedentary counterparts. Of note, analysis of mtDNA mutational load revealed no differences between exercised and sedentary groups. Collectively, these data indicate that exercise differentially influences somatic tissues of the POLG mouse as compared to oocytes, highlighting important mechanistic differences between mitochondrial regulatory mechanisms in the soma and the germline.
Highlights
In most female mammals, a natural consequence of aging is a reduction in the quantity and quality of oocytes, with the likelihood of successful pregnancy substantially diminished over time
In aged oocytes mitochondrial dysfunction becomes common, indicated by both reduction in Δψm and failure to localize to the proper perinuclear position, with mitochondrial aggregation frequently observed as a marker of poor oocyte quality (Wilding et al 2001, Selesniemi et al 2011)
The rapid accumulation of mutations generated by the defect in the proofreading-exonuclease activity of POLG in the mtDNA mutator mouse leads to a number of phenotypic defects across somatic tissues that are frequently associated with aging
Summary
A natural consequence of aging is a reduction in the quantity and quality of oocytes, with the likelihood of successful pregnancy substantially diminished over time. Upon initiation of maturation to metaphase II (MII), mitochondrial biogenesis ceases and does not resume again in the developing embryo until post implantation (Piko & Taylor 1987, Reynier et al 2001, El Shourbagy et al 2006, Santos et al 2006, Spikings et al 2007, Wai et al 2010) At this time, a subpopulation of mitochondria hyperpolarizes, resulting in an increase in mitochondrial membrane potential (Δψm) and translocates to the perinuclear region to provide the ATP required for successful meiotic spindle formation and proper chromosome segregation (Van Blerkom et al 2002). In addition to aberrant localization and Δψm, the average number of mitochondria decreases on a per-oocyte basis, concomitant with decreases in ATP biosynthesis and tricarboxylic acid cycle metabolites
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call