Decreased LONP1 expression contributes to DNA damage and meiotic defects in oocytes

IF 2.7 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Reproduction and Development Pub Date : 2023-07-01 DOI:10.1002/mrd.23694
Chuanming Liu, Manlin Xu, Yajie Guan, Lilin Li, Wenwen Liu, Bichun Guo, Xiaoqiang Sheng, Yang Zhang, Jidong Zhou, Xin Zhen, Guijun Yan, Haixiang Sun, Lijun Ding
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Abstract

Meiotic defects in oocytes are the primary reason for decreased female fertility with advanced maternal age. In this study, we revealed that decreased expression of ATP-dependent Lon peptidase 1 (LONP1) in aged oocytes and oocyte-specific depletion of LONP1 disrupt oocyte meiotic progression accompanying with mitochondrial dysfunction. In addition, LONP1 downregulation increased oocyte DNA damage. Moreover, we demonstrated that splicing factor proline and glutamine rich directly interacts with LONP1 and mediate the effect of LONP1 depletion on meiotic progression in oocytes. In summary, our data suggest that decreased expression of LONP1 is involved in advanced maternal age-related meiosis defects and that LONP1 represents a new therapeutic target to improve aged oocyte quality.

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降低LONP1表达有助于卵母细胞DNA损伤和减数分裂缺陷
卵母细胞的减数分裂缺陷是高龄产妇生育能力下降的主要原因。在这项研究中,我们发现,衰老卵母细胞中ATP依赖性Lon肽酶1(LONP1)的表达减少和卵母细胞特异性LONP1的缺失破坏了卵母细胞减数分裂进程,并伴有线粒体功能障碍。此外,LONP1下调增加了卵母细胞DNA损伤。此外,我们证明了富含脯氨酸和谷氨酰胺的剪接因子直接与LONP1相互作用,并介导LONP1缺失对卵母细胞减数分裂进程的影响。总之,我们的数据表明,LONP1表达的减少与晚期母体年龄相关的减数分裂缺陷有关,并且LONP1代表了改善衰老卵母细胞质量的一个新的治疗靶点。
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来源期刊
CiteScore
5.20
自引率
0.00%
发文量
78
审稿时长
6-12 weeks
期刊介绍: Molecular Reproduction and Development takes an integrated, systems-biology approach to understand the dynamic continuum of cellular, reproductive, and developmental processes. This journal fosters dialogue among diverse disciplines through primary research communications and educational forums, with the philosophy that fundamental findings within the life sciences result from a convergence of disciplines. Increasingly, readers of the Journal need to be informed of diverse, yet integrated, topics impinging on their areas of interest. This requires an expansion in thinking towards non-traditional, interdisciplinary experimental design and data analysis.
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