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

ABSTRACT: 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.

ORGANISM(S): Bos taurus

PROVIDER: GSE315024 | GEO | 2026/01/06

REPOSITORIES: GEO

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Project description:Despite many improvements with in vitro culture systems, the quality and developmental ability of mammalian embryos produced in vitro is still lower than their in vivo counterparts. To bring knowledge to answer this question, we used a mass spectrometry (MS) approach to compare the protein content of bovine embryos that were conceived in vivo or produced in vitro. A total of 38 pools of grade-1 quality bovine embryos at the 4-6 cell, 8-12 cell, morula, compact morula and blastocyst stages developed either in vivo or in vitro were analyzed by nano-liquid chromatography coupled with label-free quantitative mass spectrometry, allowing the identification of 3,028 proteins. Multivariate analysis of quantified proteins showed a clear separation of embryo pools according to their in vivo or in vitro origin at all stages. Three clusters of differentially abundant proteins (DAPs) according to embryo origin were evidenced, including 463 proteins more abundant in vivo than in vitro across development, and 314 and 222 proteins more abundant in vitro than in vivo before and after the morula stage, respectively. The functional analysis of proteins found more abundant in vivo showed an enrichment in carbohydrate metabolism and cytoplasmic cellular components. Proteins found more abundant in vitro before the morula stage were mostly localized in mitochondrial matrix and involved in ATP-dependent activity while those overabundant after morula stage were mostly localized in the ribonucleoprotein complex and involved in protein synthesis. Oviductin and other proteins previously shown to interact with early embryos in vitro were among the most overabundant proteins after in vivo development. In conclusion, the maternal environment led to faster degradation of mitochondrial proteins at early embryo developmental stages, lower abundance of proteins involved in protein synthesis at the time of embryonic genome activation and a global upregulation of carbohydrate and small molecule metabolic pathways compared to in vitro produced embryos. Furthermore, our data confirm that embryos developed in vivo uptake large amounts of oviduct fluid-derived proteins as soon as the 4-6 cell stage. These data provide new insight into the molecular contribution of the mother to the developmental ability of early embryos and will help designing better in vitro culture systems.

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

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