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c-Abl在小鼠植入前胚胎发育以及与mTERT表达降低相关的失调中起重要作用。

c-Abl Plays an Important Role in Mouse Preimplantation Embryo Development and the Dysregulation Associated With Decreased mTERT Expression.

作者信息

Yildirim Ecem, Onel Tugce, Yaba Aylin

机构信息

Department of Histology and Embryology, University of Health Sciences, Faculty of Medicine, İstanbul, Turkiye.

Department of Histology and Embryology, Faculty of Medicine, Demiroglu Bilim University, Istanbul, Turkiye.

出版信息

Mol Reprod Dev. 2025 Jun;92(6):e70039. doi: 10.1002/mrd.70039.

Abstract

c-Abl encodes a cytoplasmic and nuclear protein tyrosine kinase that has been implicated in processes of cell growth, proliferation, differentiation, division, and regulation of cytoskeletal structure. mTERT is a catalytic subunit of mouse telomerase and it is very important for controlling cell proliferation and homeostasis by maintaining telomere length. We demonstrated before the interaction between c-Abl and mTERT in mouse ovary and we suggested a role for c-Abl in the regulation of telomerase function and proliferation in mouse granulosa cells. The current study aims to examine the c-Abl and mTERT expression and potential interactions through mouse preimplantation embryonic development. To assess c-Abl's function in embryonic development, siRNA-mediated silencing of the c-Abl was used in mouse preimplantation embryos. After siRNA transfection, the immunofluorescence was used to examine the c-Abl pattern at embryonic development. Next, the levels of mTERT and c-Abl mRNA were compared. The results show that c-Abl is expressed in mouse preimplantation embryos at all developmental stages, with the cytoplasmic expression all through from the 2-cell to the blastocyst. Additionally, c-Abl is presented very intense expression in blastomer-blastomer junctions. The siRNA-mediated depletion of c-Abl showed developmental abnormalities at the 8- to 16-cell and morula to blastocyst and also with significantly decreased blastocyst development rate. Moreover, expression of the mTERT telomerase catalytic subunit was significantly reduced in c-Abl-depleted embryos during preimplantation embryonic development. Finally, we demonstrate that c-Abl may play a crucial role in compaction and preimplantation embryo development, and that the relationship between c-Abl and mTERT has developmental importance in early embryogenesis.

摘要

c-Abl编码一种细胞质和核蛋白酪氨酸激酶,它参与细胞生长、增殖、分化、分裂以及细胞骨架结构调节等过程。mTERT是小鼠端粒酶的催化亚基,通过维持端粒长度来控制细胞增殖和体内平衡,这一点非常重要。我们之前已证明在小鼠卵巢中c-Abl与mTERT之间存在相互作用,并提出c-Abl在小鼠颗粒细胞中端粒酶功能调节和增殖过程中发挥作用。当前研究旨在通过小鼠植入前胚胎发育来检测c-Abl和mTERT的表达及潜在相互作用。为评估c-Abl在胚胎发育中的功能,在小鼠植入前胚胎中使用了小干扰RNA(siRNA)介导的c-Abl沉默技术。siRNA转染后,利用免疫荧光检测胚胎发育过程中c-Abl的模式。接下来,比较mTERT和c-Abl mRNA的水平。结果显示,c-Abl在小鼠植入前胚胎的所有发育阶段均有表达,从2细胞期到囊胚期细胞质中一直都有表达。此外,c-Abl在卵裂球-卵裂球连接处表达非常强烈。siRNA介导的c-Abl缺失显示在8至16细胞期以及桑椹胚到囊胚期出现发育异常,囊胚发育率也显著降低。而且,在植入前胚胎发育过程中,c-Abl缺失的胚胎中端粒酶催化亚基mTERT的表达显著降低。最后,我们证明c-Abl可能在致密化和植入前胚胎发育中起关键作用,并且c-Abl与mTERT之间的关系在早期胚胎发生中具有发育重要性。

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