Chitosan alleviates ovarian aging by enhancing macrophage phagocyte-mediated tissue homeostasis.

IF 5.2 2区 医学 Q1 GERIATRICS & GERONTOLOGY
Hui-Hui Shen, Xin-Yan Zhang, Nan Liu, Yang-Yang Zhang, Hui-Hua Wu, Feng Xie, Wen-Jun Wang, Ming-Qing Li
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引用次数: 0

Abstract

Background: Age-related changes in the ovarian microenvironment are linked to impaired fertility in women. Macrophages play important roles in ovarian tissue homeostasis and immune surveillance. However, the impact of aging on ovarian macrophage function and ovarian homeostasis remains poorly understood.

Methods: Senescence-associated beta-galactosidase staining, immunohistochemistry, and TUNEL staining were used to assess senescence and apoptosis, respectively. Flow cytometry was employed to evaluate mitochondrial membrane potential (MMP) and apoptosis in granulosa cells lines (KGN), and macrophages phagocytosis. After a 2-month treatment with low molecular weight Chitosan (LMWC), ovarian tissues from mice were collected for comprehensive analysis.

Results: Compared with the liver and uterus, the ovary displayed accelerated aging in an age-dependent manner, which was accompanied by elevated levels of inflammatory factors and apoptotic cells, and impaired macrophage phagocytic activity. The aged KGN cells exhibited elevated reactive oxygen species (ROS) and apoptotic levels alongside decreased MMP. H2O2-induced aging macrophages showed reduced phagocytosis function. Moreover, there were excessive aging macrophages with impaired phagocytosis in the follicular fluid of patients with diminished ovarian reserve (DOR). Notably, LMWC administration alleviated ovarian aging by enhancing macrophage phagocytosis and promoting tissue homeostasis.

Conclusions: Aging ovarian is characterized by an accumulation of aging and apoptotic granulosa cells, an inflammatory response and macrophage phagocytosis dysfunction. In turn, impaired phagocytosis of macrophage contributes to insufficient clearance of aging and apoptotic granulosa cells and the increased risk of DOR. Additionally, LMWC emerges as a potential therapeutic strategy for age-related ovarian dysfunction.

壳聚糖通过增强巨噬细胞吞噬细胞介导的组织稳态来缓解卵巢衰老。
背景:卵巢微环境中与年龄相关的变化与女性生育能力受损有关。巨噬细胞在卵巢组织稳态和免疫监视中发挥着重要作用。然而,人们对衰老对卵巢巨噬细胞功能和卵巢稳态的影响仍知之甚少:方法:采用衰老相关的β-半乳糖苷酶染色法、免疫组化法和TUNEL染色法分别评估衰老和细胞凋亡。流式细胞术用于评估粒细胞系(KGN)的线粒体膜电位(MMP)和凋亡情况,以及巨噬细胞的吞噬能力。用低分子量壳聚糖(LMWC)治疗 2 个月后,收集小鼠卵巢组织进行综合分析:结果:与肝脏和子宫相比,卵巢的衰老速度呈年龄依赖性,伴随着炎症因子和凋亡细胞水平的升高,以及巨噬细胞吞噬活性的减弱。老化的KGN细胞表现出活性氧(ROS)和细胞凋亡水平升高,同时MMP下降。H2O2- 诱导的老化巨噬细胞的吞噬功能降低。此外,在卵巢储备功能减退(DOR)患者的卵泡液中存在过多的老化巨噬细胞,其吞噬功能受损。值得注意的是,服用低密度脂蛋白胆固醇可通过增强巨噬细胞的吞噬功能和促进组织稳态来缓解卵巢衰老:结论:衰老卵巢的特征是衰老和凋亡颗粒细胞的积累、炎症反应和巨噬细胞吞噬功能障碍。反过来,巨噬细胞吞噬功能受损也会导致衰老和凋亡的颗粒细胞清除不足,增加罹患 DOR 的风险。此外,低密度脂蛋白胆固醇还可作为一种潜在的治疗策略,用于治疗与年龄有关的卵巢功能障碍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Immunity & Ageing
Immunity & Ageing GERIATRICS & GERONTOLOGY-IMMUNOLOGY
CiteScore
10.20
自引率
3.80%
发文量
55
期刊介绍: Immunity & Ageing is a specialist open access journal that was first published in 2004. The journal focuses on the impact of ageing on immune systems, the influence of aged immune systems on organismal well-being and longevity, age-associated diseases with immune etiology, and potential immune interventions to increase health span. All articles published in Immunity & Ageing are indexed in the following databases: Biological Abstracts, BIOSIS, CAS, Citebase, DOAJ, Embase, Google Scholar, Journal Citation Reports/Science Edition, OAIster, PubMed, PubMed Central, Science Citation Index Expanded, SCImago, Scopus, SOCOLAR, and Zetoc.
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