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炎症衰老：分子表型的扩展及其在年龄相关女性不孕症中的作用

Inflammaging: Expansion of Molecular Phenotype and Role in Age-Associated Female Infertility.

作者信息

Ivanov Dmitry, Drobintseva Anna, Rodichkina Valeriia, Mironova Ekaterina, Zubareva Tatyana, Krylova Yuliya, Morozkina Svetlana, Marasco Maria Greta Pia, Mazzoccoli Gianluigi, Nasyrov Ruslan, Kvetnoy Igor

机构信息

Deportment of Medical Biology, Saint-Petersburg State Pediatric Medical University, Litovskaya Ulitsa, 2, 194100 Saint Petersburg, Russia.

Saint-Petersburg Research Institute of Phthisiopulmonology, Ligovsky pr., 2-4, 191036 Saint Petersburg, Russia.

出版信息

Biomedicines. 2024 Sep 2;12(9):1987. doi: 10.3390/biomedicines12091987.

DOI:10.3390/biomedicines12091987
PMID:39335502
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11428237/
Abstract

Cellular aging is considered as one of the main factors implicated in female infertility. We evaluated the expression of senescence-associated secretory phenotype (SASP) markers and additional molecular factors in an in vitro model of cellular aging. We induced genotoxic stress (UVB/UVA ray irradiation) in primary human endometrial cells obtained from female subjects of young reproductive age (<35 years of age). We assessed the expression levels of IL-6, IL-8, IL-1α, MMP3, SIRT-1, SIRT-6, TERF-1, and CALR at the mRNA level by RT-qPCR and at the protein level by immunofluorescence and confocal microscopy in primary human endometrial cells upon induction of genotoxic stress and compared them to untreated cells. Statistically significant differences were found for the expression of SIRT-1, SIRT-6, and TERF, which were found to be decreased upon induction of cell senescence through genotoxic stress, while IL-6, IL-8, IL-1α, MMP3, and p16 were found to be increased in senescent cells. We propose that these molecules, in addition to SAS-linked factors, could represent novel markers, and eventually potential therapeutic targets, for the aging-associated dysfunction of the female reproductive system.

摘要

细胞衰老被认为是女性不孕的主要因素之一。我们在细胞衰老的体外模型中评估了衰老相关分泌表型（SASP）标志物和其他分子因子的表达。我们对从年轻育龄女性（<35岁）受试者获得的原代人子宫内膜细胞施加基因毒性应激（UVB/UVA射线照射）。我们通过RT-qPCR在mRNA水平以及通过免疫荧光和共聚焦显微镜在蛋白水平评估了基因毒性应激诱导后原代人子宫内膜细胞中IL-6、IL-8、IL-1α、MMP3、SIRT-1、SIRT-6、TERF-1和CALR的表达水平，并将它们与未处理的细胞进行比较。发现SIRT-1、SIRT-6和TERF的表达存在统计学显著差异，通过基因毒性应激诱导细胞衰老后它们的表达降低，而IL-6、IL-8、IL-1α、MMP3和p16在衰老细胞中表达增加。我们提出，除了与SASP相关的因子外，这些分子可能代表女性生殖系统衰老相关功能障碍的新型标志物，并最终成为潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da7/11428237/af42e84a1412/biomedicines-12-01987-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da7/11428237/d0d70e73ee38/biomedicines-12-01987-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da7/11428237/f2deea122035/biomedicines-12-01987-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da7/11428237/9c7e4fe2581e/biomedicines-12-01987-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da7/11428237/19c3a8bb456f/biomedicines-12-01987-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da7/11428237/af42e84a1412/biomedicines-12-01987-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da7/11428237/d0d70e73ee38/biomedicines-12-01987-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da7/11428237/f2deea122035/biomedicines-12-01987-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da7/11428237/9c7e4fe2581e/biomedicines-12-01987-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da7/11428237/19c3a8bb456f/biomedicines-12-01987-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da7/11428237/af42e84a1412/biomedicines-12-01987-g005.jpg

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