Chicco 2018 MiP2018a
Accumulating evidence indicates that an inability of oocyte mitochondria to meet the energy demands of maturation, fertilization, and embryo development contributes to infertility, chromosomal abnormalities and poor assisted reproduction outcomes . This is particularly relevant in the context of maternal aging, where a loss of oocyte mitochondrial content is thought to limit oxidative phosphorylation (OXPHOS) capacity secondary to reductions in mtDNA content or replication . However, our understanding of oocyte and embryo energy metabolism has been limited by technical challenges of sample paucity, and so is based largely on indirect estimates of mitochondrial capacity/content and metabolite analyses. To overcome this limitation, our team developed a miniaturized metabolic multi-sensor capable of real-time monitoring of oxygen consumption and glycolytic flux (glucose, lactate and pH) in single oocytes and embryos. Using this new technology in bovine samples, we characterized the time-course of metabolic changes that occur from oocyte maturation to the blastocyst stage, demonstrating a progressive increase in the utilization of glycolysis over OXPHOS to support energy demands during these stages of development. In equine subjects, we found that oocyte OXPHOS rates decline with maternal age, but with inconsistent loss of maximal (CCCP-induced) respiratory capacity, suggesting a possible age-related shift in metabolic substrate utilization. In parallel studies of equine granulosa cell metabolism using high-resolution respirometry and fluorometry, we found that maternal aging does not impair OXPHOS capacity, but increases release of mitochondria-derived reactive oxygen species (ROS), consistent with evidence that follicular ROS compromises oocyte function and fertilization potential in human aging . These results provide the basis for ongoing efforts to establish new methodology and instrumentation for integrative metabolic monitoring of oocyte and embryo development that enables scientific and therapeutic advances in human reproductive fitness and assisted reproduction outcomes.
Labels: MiParea: Respiration Pathology: Aging;senescence
Organism: Horse Tissue;cell: Genital
Coupling state: OXPHOS, ET
HRR: Oxygraph-2k, O2k-Fluorometer
Chicco AJ(1,3), Obediat Y(2,3), Catandi GD(1), Carnevale EM(1), Chen T(2,3)
- College Veterinary Medicine Biomedical Sciences
- Dept Electrical Computer Engineering
- School Biomedical Engineering, Colorado State Univ, Fort Collins, CO, USA. - [email protected]
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