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Theriogenology. 2025 Aug 9;249:117631. doi: 10.1016/j.theriogenology.2025.117631. Online ahead of print.
ABSTRACT
Oocyte-stored maternal factors are critical for successful embryonic development, but they are remained incompletely understood. Histone demethylase KDM5B has been implicated in the regulation of embryonic development and genomic stability. However, the specific role of KDM5B during oocyte maturation and early embryogenesis remains unclear in goat. In this study, we investigated the function of KDM5B during goat oocyte maturation and early embryogenesis. Using GSK467, a selective KDM5B inhibitor, we observed increased H3K4me3 accumulation in both oocytes and parthenogenetically activated (PA) embryos. Secondly, inhibition of KDM5B disrupted spindle assembly and chromosome alignment, induced DNA damage, and significantly reduced the oocyte maturation rate in both goat and mouse models. Moreover, inhibition of KDM5B leads to developmental arrest of PA embryos, and low-input RNA sequencing of 8-cell-stage PA embryos revealed defective maternal mRNA degradation and impaired zygotic genome activation. In summary, our findings demonstrate that KDM5B plays a critical role in regulating spindle assembly and chromosome alignment maintaining oocyte quality, and supporting early embryo development. This study provides new insights into the epigenetic regulation of reproductive competence in mammals.
PMID:40803156 | DOI:10.1016/j.theriogenology.2025.117631