The Effect of PDSS2, a Component of the Coenzyme Q Biosynthetic Pathway, on Murine Oocyte Embryo Development

Female reproductive capacity dramatically declines with age. Decrease in oocyte number and quality is primarily responsible for this phenomenon. However, although multiple theories of reproductive aging have been proposed, the exact cause of oocyte quality decline remains unclear. One factor that seems to contribute is the reduced availability of coenzyme Q (coQ), a component of the mitochondrial respiratory chain, as it has been previously shown that both transcript and protein expression of various coQ biosynthetic enzymes decrease in aged murine oocytes. To further explore the impact of coQ deficiency on female fertility, we generated a mouse line harbouring an oocyte-specific deletion of Pdss2 and sought to fully characterize its phenotypes. Pdss2-deficient females recapitulated many hallmarks of reproductive aging, such as low ovulation rates and inability to produce litters. Embryonic health was also drastically reduced, and most Pdss2-deficient embryos arrested at the 2-to 4-cell stage during in vitro development. Highlighting the importance of coQ and Pdss2 in the maintenance of mitochondrial health, oocytes and 2-cell embryos from Pdss2-deficient females had compromised mitochondrial function and decreased mitochondrial endowment. Furthermore, Pdss2-deficient 2-cell embryos failed to undergo maternal-to-zygotic transition (MZT) during early embryogenesis, displaying aberrant epigenetic landscapes and accumulation of maternal factors. They also displayed aberrant mTOR signaling, as was previously observed in somatic tissue of Pdss2 mutant mice. To ameliorate symptoms of oocyte-specific Pdss2 deficiency, in vivo coQ supplementation was provided via drinking water, as well as another mitochondrial bioenergetic, pyrroloquinoline quinone (PQQ). Interestingly, PQQ supplementation was able to increase the proportion of d3.5 Pdss2-deficient embryos at the morula/blastocyst stage and litter production rates of Pdss2-deficient females, although coQ could not. We found PQQ can improve oocyte and embryo mitochondrial function, but it is not yet clear why PQQ is a more effective treatment than coQ. Further understanding of the impact of PDSS2 and PQQ on the developmental capacity of oocytes and early embryos will help elucidate the pathogenesis underlying oocyte aging and contribute to development of effective assisted reproductive techniques.

Department dc:contributor.department

Physiology

Year dc:date.issued

2023

Author dc:creator

• Kim, Kyunga

Advisor dc:contributor.advisor

• Jurisicova, Andrea

• Coenzyme Q
• Female fertility
• Mitochondria
• Reproductive aging
• Ubiquinone

Handle dc:identifier.uri

https://hdl.handle.net/1807/144529

OAI identifier oai:identifier

oai:utoronto.scholaris.ca:1807/144529