Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Dynamic regulation of telomerase expression and activity during preimplantation embryogenesis is perturbed by oxidative stress. (#430)

Yasmyn E Winstanley 1 , Donna L Holland 1 , Thao Dinh 1 , Darryl L Russell 1 , Rebecca L Robker 1
  1. Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia

Telomeres, the protective DNA sequences at chromosome ends, shorten with every cell division. Short telomeres trigger cellular senescence and diminished tissue function. Therefore, telomere length must be regenerated in offspring to ensure viability and health of the next generation. Telomere elongation in preimplantation embryos is largely mediated by the telomerase enzyme complex; however little is known about the regulation of this process. To address this, we investigated expression levels of telomere regulatory genes through an unbiased in silico approach and targeted analysis of candidate genes, as well as enzyme activity, during preimplantation development. Firstly, expression of telomere regulatory genes was assessed in RNA-seq datasets of mouse, macaque, and human preimplantation embryos. Dynamic patterns of gene expression were observed; in particular, a large cohort of genes was upregulated between the 8-cell and blastocyst, when telomere elongation is maximal. Next, expression of telomerase complex genes (Tert, Terc, Dck1) was analysed in mouse embryos (8-cell, morula, blastocyst, inner cell mass (ICM)) using RT-qPCR, and telomerase activity assays conducted in parallel cohorts. Surprisingly, expression of telomerase genes decreased with each successive stage of preimplantation development, while telomerase activity increased, concurrent with telomere elongation. Telomerase gene expression was highest in the blastocyst ICM, consistent with longer telomeres in these cells. Building on our recent findings that oocyte oxidative stress impairs telomere elongation in embryos, we examined whether this was due to altered telomerase complex gene expression or enzymatic activity. Mice were fed rotenone (to induce mtROS in oocytes), and preimplantation embryos analyzed. In 8-cell embryos Tert, Terc, and Dck1 expression and telomerase activity increased in response to rotenone-induced oxidative stress, however expression in the latter stages of development was unaffected. These results provide new information about the regulation of telomere-associated genes throughout preimplantation development and mechanisms of telomere length inheritance, which ultimately influence offspring aging.