PDF(Pubmed)
Abstract：
BACKGROUND: Helicase for meiosis 1 (HFM1), a putative DNA helicase expressed in germ-line cells, has been reported to be closely associated with premature ovarian insufficiency (POI). However, the underlying molecular mechanism has not been clearly elucidated. The aim of this study was to investigate the function of HFM1 in the first meiotic prophase of mouse oocytes.
RESULTS: The results suggested that the deficiency of HFM1 resulting in increased apoptosis and depletion of oocytes in mice, while the oocytes were arrested in the pachytene stage of the first meiotic prophase. In addition, impaired DNA double-strand break repair and disrupted synapsis were observed in the absence of HFM1. Further investigation revealed that knockout of HFM1 promoted ubiquitination and degradation of FUS protein mediated by FBXW11. Additionally, the depletion of HFM1 altered the intranuclear localization of FUS and regulated meiotic- and oocyte development-related genes in oocytes by modulating the expression of BRCA1.
CONCLUSIONS: These findings elaborated that the critical role of HFM1 in orchestrating the regulation of DNA double-strand break repair and synapsis to ensure meiosis procession and primordial follicle formation. This study provided insights into the pathogenesis of POI and highlighted the importance of HFM1 in maintaining proper meiotic function in mouse oocytes.
RESULTS: The results suggested that the deficiency of HFM1 resulting in increased apoptosis and depletion of oocytes in mice, while the oocytes were arrested in the pachytene stage of the first meiotic prophase. In addition, impaired DNA double-strand break repair and disrupted synapsis were observed in the absence of HFM1. Further investigation revealed that knockout of HFM1 promoted ubiquitination and degradation of FUS protein mediated by FBXW11. Additionally, the depletion of HFM1 altered the intranuclear localization of FUS and regulated meiotic- and oocyte development-related genes in oocytes by modulating the expression of BRCA1.
CONCLUSIONS: These findings elaborated that the critical role of HFM1 in orchestrating the regulation of DNA double-strand break repair and synapsis to ensure meiosis procession and primordial follicle formation. This study provided insights into the pathogenesis of POI and highlighted the importance of HFM1 in maintaining proper meiotic function in mouse oocytes.
摘要：
背景：减数分裂1（HFM1）的解旋酶，在生殖系细胞中表达的推定DNA解旋酶，据报道，与卵巢早衰（POI）密切相关。然而,潜在的分子机制尚未明确阐明。这项研究的目的是研究HFM1在小鼠卵母细胞的第一个减数分裂前期的功能。
结果：结果表明，HFM1缺乏导致小鼠卵母细胞凋亡和耗竭增加，而卵母细胞在第一个减数分裂前期的粗线期被捕。此外,在没有HFM1的情况下，观察到受损的DNA双链断裂修复和破坏的突触。进一步的研究表明，HFM1的敲除促进了FBXW11介导的FUS蛋白的泛素化和降解。此外,HFM1的缺失改变了FUS的核内定位，并通过调节BRCA1的表达来调节卵母细胞中减数分裂和卵母细胞发育相关基因。
结论：这些发现阐述了HFM1在协调DNA双链断裂修复和突触调节以确保减数分裂进程和原始卵泡形成方面的关键作用。这项研究提供了对POI发病机理的见解，并强调了HFM1在维持小鼠卵母细胞适当减数分裂功能中的重要性。
结果：结果表明，HFM1缺乏导致小鼠卵母细胞凋亡和耗竭增加，而卵母细胞在第一个减数分裂前期的粗线期被捕。此外,在没有HFM1的情况下，观察到受损的DNA双链断裂修复和破坏的突触。进一步的研究表明，HFM1的敲除促进了FBXW11介导的FUS蛋白的泛素化和降解。此外,HFM1的缺失改变了FUS的核内定位，并通过调节BRCA1的表达来调节卵母细胞中减数分裂和卵母细胞发育相关基因。
结论：这些发现阐述了HFM1在协调DNA双链断裂修复和突触调节以确保减数分裂进程和原始卵泡形成方面的关键作用。这项研究提供了对POI发病机理的见解，并强调了HFM1在维持小鼠卵母细胞适当减数分裂功能中的重要性。
