Virtual Presentation SRB Virtual Awards 2020

Telomere elongation kinetics during embryogenesis are dysregulated by maternal obesity and age (#14)

Yasmyn E Gordon 1 , Darryl L Russell 1 , Rebecca L Robker 1
  1. The Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia

Telomeres are repetitive DNA sequences at the chromosome ends that control cell cycle, cellular lifespan and genome integrity. Telomere length is an important determinant of health, with short telomeres associated with adverse pathologies and short lifespan. Telomeres shorten with every cell division, therefore telomere length must be regenerated in offspring to ensure viability of each new generation. This study characterised telomere elongation mechanisms during preimplantation development and the impact of maternal ageing or obesity which are known to negatively influence embryogenesis. A qPCR assay measuring telomere length in individual mouse oocytes and embryos was developed and revealed normal telomere elongation occuring in two phases, rapidly within the first three cell divisions and at the blastocyst stage. Parthenotes exhibited telomere elongation indicating the necessary factors are present in the oocyte. A panel of telomere binding and extension factors showed dynamic expression patterns throughout embryogenesis. We compared this process in young/lean, versus reproductively aged or obese females. Viability (fragmentation, maturity) of oocytes from young/lean, reproductively aged (~12 months old) or obese (5.5 months, >36g) females was not different, yet oocytes from obese and old females had shorter telomeres. Following IVF, 8C stage telomere lengths had normalised in embryos from obese and older females. Subsequent embryo development kinetics was also similar between groups yet total blastocyst cell numbers (both Oct4+ and Cdx2+) were decreased in embryos conceived from obese or old oocytes compared to controls. Importantly, the per cell telomere length was significantly shorter in blastocyst stage embryos from oocytes of obese or older females indicating deficient telomere resetting in these offspring. Thus, telomere elongation patterns are dynamically regulated during pre-implantation embryogenesis via distinct mechanisms. Further, telomere resetting is significantly altered with female obesity and reproductive ageing, and likely contributes to the poorer health outcomes, including reduced lifespan, seen in offspring.