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在老年小鼠中,cGAS-STING通路的激活会导致异常的子宫受体

Si-Ting Chen^1,2,3, Wen-Wen Shi³, Feng Ran^1,2

¹Key Laboratory of Plateau Mountain Animal Genetics, Breeding and Reproduction, Ministry of Education, Guizhou University, Guiyang, China.

|August 8, 2024

概括

由于PROGERIN的积累,DNA泄漏和STING通路的激活,母亲的衰老会损害子宫的受容性和胚胎植入. 这些变化缩小了子宫.

科学领域:

生殖生物学生殖生物学
细胞衰老细胞衰老
基因组学就是基因组学.

背景情况:

母亲年龄显著影响怀孕成功,子宫衰老是老年妇女失败的主要原因.
子宫衰老影响子宫受体和决定性的精确机制在很大程度上是未知的.

研究的目的:

调查母亲老龄化对子宫受体性和胚胎植入老老鼠的影响.
阐明与年龄相关的子宫功能障碍背后的分子机制.

主要方法:

利用自然年龄 (一岁) 的雌性小鼠来评估胚胎植入.
在子宫组织中分析了核和细胞质蛋白质水平 (LAMIN A,PRELAMIN A,PROGERIN) 和DNA完整性.
研究了cGAS-STING通路,DNAse活性,雌激素水平和CD14在老鼠子宫中的作用.
在体外和体内使用DNA,STING激动剂/抑制剂,雌激素和CD14的治疗.

主要成果:

年龄较大的小鼠表现出异常的子宫受容性,其特征是核LAMIN A的减少和PRELAMIN A和PROGERIN的增加.
在老老鼠子宫中观察到细胞质双链DNA (dsDNA) 的显著积累.
的过度表达导致核DNA泄漏和子宫受体能力受损.
在老年子宫中,DNA降解酶 (DNase I,DNase II,TREX1) 的活性降低.
激活cGAS-STING通路和增加子宫雌激素 (E2) 和CD14水平与衰老有关.
模仿外来DNA或激活STING的治疗,高E2和CD14受损子宫受体性标志物和胚胎植入.

结论:

在老年小鼠中,子宫PROGERIN的增加会导致细胞质DNA的积累,并激活cGAS-STING通路,从而损害子宫的受容性.
老年子宫中CD14分泌量的增加进一步损害了胚胎植入.
在老年小鼠中,STING通路的抑制部分挽救了子宫异常,这表明了治疗点.

关键词:

CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 CD14 衰老的衰老衰老的衰老 cGAS-STING 的使用情况.孕产妇的孕产物是什么子宫的感受性子宫的感受性

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