Species-Specific Telomere Length Differences Between Blastocyst Cell Compartments and Ectopic Telomere Extension in Early Bovine Embryos by Human Telomerase Reverse Transcriptase

The enzyme telomerase is active in germ cells and is critically involved in maintenance of telomere length in successive generations. In preimplantation mammalian embryos, telomerase activity is present from the morula stage onward and is associated with an increase in telomere length in blastocysts. Here, we show that telomere length regulation in murine and bovine blastocysts differed between trophectodermal and inner cell mass cells in a species-specific manner. Ectopic expression of human telomerase reverse transcriptase (human TER1) in bovine embryos increased telomerase activity and in turn increased telomere length. Transient expression of human TERT could be targeted either to the 4-cell- to the morula stage, or to morula-to-blastocyst stages by employing unmodified or cytosine methylated expression plasmids, respectively. In conclusion, introduction of human TERT constructs in bovine embryos resulted in functional telomerase expression and effective telomere elongation, allowing to studying the consequences on embryonic development. Ultimately, these studies might lead to a large animal model for telomere regulation and aging.

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