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cGAS-STING 通路的激活导致老年小鼠子宫容受性异常。

The activation of cGAS-STING pathway causes abnormal uterine receptivity in aged mice.

机构信息

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

College of Animal Science, Guizhou University, Guiyang, China.

出版信息

Aging Cell. 2024 Nov;23(11):e14303. doi: 10.1111/acel.14303. Epub 2024 Aug 7.

DOI:10.1111/acel.14303
PMID:39113346
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11561655/
Abstract

Maternal age is one of the most important factors affecting the success of maternal pregnancy. Uterine aging is the leading cause of pregnancy failure in older women. However, how uterine aging affects uterine receptivity and decidualization is unclear. In this study, naturally aged one-year-old female mice were used to investigate effects of maternal age on embryo implantation during early pregnancy. In our study, we found abnormal uterine receptivity in aged mice. Aged mouse uterus indicates a decrease in nuclear LAMIN A, and an increase in PRELAMIN A and PROGERIN. In aged mouse uterus, double-stranded DNA (dsDNA) in cytoplasmic fraction is significantly increased. PROGERIN overexpression in mouse uterine epithelial cells and epithelial organoids leads to nuclear DNA leakage and impaired uterine receptivity. DNase I, DNase II, and TREX1 are obviously reduced in aged mouse uterus. Treatments with foreign DNA or STING agonist significantly downregulate uterine receptivity markers and activate cGAS-STING pathway. Uterine estrogen (E) concentration is significantly increased in aged mice. After ovariectomized mice are treated with a high level of E, there are significant increase of PROGERIN and cytoplasmic DNA, and activation of cGAS-STING pathway. CD14 is significantly increased in aged uterus. Intrauterine CD14 injection inhibits embryo implantation. In vitro CD14 treatment of cultured epithelial cells or epithelial organoids decreases uterine receptivity. Uterine abnormality in aged mouse can be partially rescued by STING inhibitor. In conclusion, uterine PROGERIN increase in aged mouse uterus results in cytoplasmic DNA accumulation and cGAS-STING pathway activation. CD14 secretion in aged uterus impairs uterine receptivity.

摘要

母体年龄是影响妊娠成功的最重要因素之一。子宫衰老（aging）是老年妇女妊娠失败的主要原因。然而，子宫衰老如何影响子宫容受性和蜕膜化尚不清楚。在本研究中，使用自然衰老的一岁雌性小鼠来研究母体年龄对妊娠早期胚胎着床的影响。在我们的研究中，我们发现衰老小鼠的子宫容受性异常。衰老小鼠的子宫表现为核层粘连蛋白 A（LAMIN A）减少，前层粘连蛋白 A（PRELAMIN A）和早熟素（PROGERIN）增加。衰老小鼠子宫细胞质部分的双链 DNA（dsDNA）显著增加。在小鼠子宫上皮细胞和上皮类器官中过表达 PROGERIN 导致核 DNA 泄漏和子宫容受性受损。衰老小鼠子宫中的 DNase I、DNase II 和 TREX1 明显减少。用外源 DNA 或 STING 激动剂处理可显著下调子宫容受性标志物并激活 cGAS-STING 途径。衰老小鼠子宫中的雌激素（E）浓度显著增加。对去卵巢小鼠用高水平 E 处理后，PROGERIN 和细胞质 DNA 显著增加，cGAS-STING 途径被激活。衰老子宫中的 CD14 明显增加。宫内注射 CD14 抑制胚胎着床。体外 CD14 处理培养的上皮细胞或上皮类器官可降低子宫容受性。衰老小鼠的子宫异常可部分通过 STING 抑制剂得到挽救。总之，衰老小鼠子宫中的 PROGERIN 增加导致细胞质 DNA 积累和 cGAS-STING 途径激活。衰老子宫中 CD14 的分泌损害了子宫容受性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a590/11561655/e2016371d6bd/ACEL-23-e14303-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a590/11561655/4f1d23bfe509/ACEL-23-e14303-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a590/11561655/236c65765b91/ACEL-23-e14303-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a590/11561655/5efa68bc9381/ACEL-23-e14303-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a590/11561655/162e7316290a/ACEL-23-e14303-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a590/11561655/952207f666a7/ACEL-23-e14303-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a590/11561655/e2016371d6bd/ACEL-23-e14303-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a590/11561655/4f1d23bfe509/ACEL-23-e14303-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a590/11561655/03ad09dbf2da/ACEL-23-e14303-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a590/11561655/6c6358fef1ff/ACEL-23-e14303-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a590/11561655/236c65765b91/ACEL-23-e14303-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a590/11561655/5efa68bc9381/ACEL-23-e14303-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a590/11561655/162e7316290a/ACEL-23-e14303-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a590/11561655/952207f666a7/ACEL-23-e14303-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a590/11561655/e2016371d6bd/ACEL-23-e14303-g003.jpg

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本文引用的文献

1
Metabolic pathways in immune senescence and inflammaging: Novel therapeutic strategy for chronic inflammatory lung diseases. An EAACI position paper from the Task Force for Immunopharmacology.免疫衰老和炎症老化中的代谢途径：慢性炎症性肺部疾病的新治疗策略。来自免疫药理学工作组的 EAACI 立场文件。
Allergy. 2024 May;79(5):1089-1122. doi: 10.1111/all.15977. Epub 2023 Dec 18.
2
Peripheral inflammation and neurocognitive impairment: correlations, underlying mechanisms, and therapeutic implications.外周炎症与神经认知障碍：相关性、潜在机制及治疗意义。
Front Aging Neurosci. 2023 Nov 29;15:1305790. doi: 10.3389/fnagi.2023.1305790. eCollection 2023.
3
Int J Mol Sci. 2025 Apr 26;26(9):4122. doi: 10.3390/ijms26094122.
A new fluorescent probe for the visualization of progerin.
用于异常蛋白可视化的新型荧光探针。
Bioorg Chem. 2024 Jan;142:106967. doi: 10.1016/j.bioorg.2023.106967. Epub 2023 Nov 11.
4
Dingkun pill alleviates metabolic abnormalities in polycystic ovary syndrome through brown adipose tissue activation.定坤丹通过激活棕色脂肪组织缓解多囊卵巢综合征的代谢异常。
J Ovarian Res. 2023 Aug 26;16(1):176. doi: 10.1186/s13048-023-01215-0.
5
cGAS-STING drives ageing-related inflammation and neurodegeneration.cGAS-STING 驱动与衰老相关的炎症和神经退行性变。
Nature. 2023 Aug;620(7973):374-380. doi: 10.1038/s41586-023-06373-1. Epub 2023 Aug 2.
6
Endometrial receptivity in women of advanced age: an underrated factor in infertility.高龄女性的子宫内膜容受性：不孕的一个被低估的因素。
Hum Reprod Update. 2023 Nov 2;29(6):773-793. doi: 10.1093/humupd/dmad019.
7
Embryo-derive TNF promotes decidualization via fibroblast activation.胚胎源 TNF 通过激活成纤维细胞促进蜕膜化。
Elife. 2023 Jul 17;12:e82970. doi: 10.7554/eLife.82970.
8
Subclinical atherosclerosis and accelerated epigenetic age mediated by inflammation: a multi-omics study.亚临床动脉粥样硬化和炎症介导的表观遗传年龄加速：一项多组学研究。
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9
Identification of epigenetic modulators as determinants of nuclear size and shape.鉴定表观遗传调节剂作为核大小和形状的决定因素。
Elife. 2023 May 23;12:e80653. doi: 10.7554/eLife.80653.
10
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