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

Telomere length (TL) is an important indicator of embryo quality and is associated with subsequent developmental outcomes. However, little is known about the factors that regulate TL during embryonic development. Because in vitro-produced embryos typically exhibit shorter TL than in vivo-developed embryos, this study aimed to identify factors that regulate TL in bovine embryos. Candidate regulators were identified by integrating RNA-seq data from bovine blastocysts with normal or short TL and information on factors present in oviductal fluid. Ingenuity Pathway Analysis of differentially expressed genes identified angiotensin II (Ang II), transforming growth factor-beta 1 (TGFB1), and epidermal growth factor (EGF) as candidate regulators. The effects of supplementing these factors in the culture medium were then evaluated with respect to embryonic development, TL, telomerase activity, and DNA methylation. All three factors improved embryonic development. Ang II and TGFB1 increased TL at the blastocyst stage and reduced global DNA methylation levels at both the 8-cell and blastocyst stages. Transcriptomic analysis further suggested that Ang II and TGFB1 modulated pathways related to chromatin remodeling and telomere maintenance. These findings identify Ang II and TGFB1 as important regulators of telomere length during bovine preimplantation development and suggest that their effects are mediated, at least in part, through epigenetic remodeling.