Angiotensin II and TGFB1 Induce Global DNA Demethylation and Telomere Elongation in Bovine Embryos

Abstract

Simple Summary Telomere length (TL) is an important marker of embryo quality, but the factors affecting TL during embryonic development are not well understood. In vitro-produced embryos exhibit shorter TL than in vivo-developed embryos. In this study, we investigated factors that may extend TL in bovine embryos. Using RNA-seq analysis, we identified three candidate factors: angiotensin II (Ang II), transforming growth factor-beta 1 (TGFB1), and epidermal growth factor (EGF). Supplementation with these factors improved embryonic development only when administered from the zygote to the 8-cell stage, whereas treatment initiated after the 8-cell stage produced no detectable phenotypic changes. Early treatment also induced global DNA demethylation and enhanced telomere elongation at the blastocyst stage. Concomitantly, reduced levels of protection of telomeres 1 (POT1) and increased histone acetylation levels were observed in embryos. These findings suggest that Ang II and TGFB1 support embryonic development in association with epigenetic modifications and telomere elongation.