Histone lactylation maintains bovine early embryo development via regulating embryonic genome activation [scRNA-Seq]

Early embryo loss is an important factor affecting the reproductive capacity of cattle. Recent studies have revealed that during the process of the embryonic genome activation (EGA), epigenetic modification, such as, histone lactylation modification remodeling is crucial for early embryonic development. However, the effect and mechanism of histone lactylation modification on bovine early embryo development remain unknown. In this study, we found that histone lactylation, including pan Kla, H3K9la, and H3K18la were mainly located in nuclear, and were significantly decreased from 8-cell to morula stage as well as increased from morula to blastocyst stage in bovine IVF embryos. Decreased or increased levels of histone lactylation by GSKA or NaLa supplementation inhibited bovine early embryo development and blastocyst lineage differentiation. Furthermore, combined with scRNA-Seq data and EU straining revealed that reduction of histone lactylation levels altered expression of genes associated with DNA transcription and RNA polymerase activity, thereby impairing the process of EGA. Importantly, NMN rescued the inhibitory effects of GSKA supplementation in bovine EGA and early embryonic development. Altogether, these results indicated that histone lactylation maintains bovine early embryo development via regulating EGA process. These findings provide theoretical references for addressing early embryo loss and thereby enhancing the reproductive capacity of cattle. Overall design: Utilizing single-cell RNA sequencing technology, we conducted an in-depth investigation into how histone lactylation modification affects bovine embryonic genome activation