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颗粒细胞洞察:揭示月经血源性干细胞及其外泌体在多囊卵巢综合征 (PCOS) 中线粒体机制中的潜力。

Granulosa cell insight: unraveling the potential of menstrual blood-derived stem cells and their exosomes on mitochondrial mechanisms in polycystic ovary syndrome (PCOS).

机构信息

Anatomical Sciences Department, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.

Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.

出版信息

J Ovarian Res. 2024 Aug 17;17(1):167. doi: 10.1186/s13048-024-01484-3.

Abstract

BACKGROUND

Polycystic ovary syndrome (PCOS) presents a significant challenge in women's reproductive health, characterized by disrupted folliculogenesis and ovulatory dysfunction. Central to PCOS pathogenesis are granulosa cells, whose dysfunction contributes to aberrant steroid hormone production and oxidative stress. Mitochondrial dysfunction emerges as a key player, influencing cellular energetics, oxidative stress, and steroidogenesis. This study investigates the therapeutic potential of menstrual blood-derived stem cells (MenSCs) and their exosomes in mitigating mitochondrial dysfunction and oxidative stress in PCOS granulosa cells.

METHODS

Using a rat model of PCOS induced by letrozole, granulosa cells were harvested and cultured. MenSCs and their exosomes were employed to assess their effects on mitochondrial biogenesis, oxidative stress, and estrogen production in PCOS granulosa cells.

RESULTS

Results showed diminished mitochondrial biogenesis and increased oxidative stress in PCOS granulosa cells, alongside reduced estrogen production. Treatment with MenSCs and their exosomes demonstrated significant improvements in mitochondrial biogenesis, oxidative stress levels, and estrogen production in PCOS granulosa cells. Further analysis showed MenSCs' superior efficacy over exosomes, attributed to their sustained secretion of bioactive factors. Mechanistically, MenSCs and exosomes activated pathways related to mitochondrial biogenesis and antioxidative defense, highlighting their therapeutic potential for PCOS.

CONCLUSIONS

This study offers insights into granulosa cells mitochondria's role in PCOS pathogenesis and proposes MenSCs and exosomes as a potential strategy for mitigating mitochondrial dysfunction and oxidative stress in PCOS. Further research is needed to understand underlying mechanisms and validate clinical efficacy, presenting promising avenues for addressing PCOS complexity.

摘要

背景

多囊卵巢综合征(PCOS)是女性生殖健康的一个重大挑战,其特征是卵泡生成和排卵功能障碍。PCOS 的发病机制的核心是颗粒细胞,其功能障碍导致异常的甾体激素产生和氧化应激。线粒体功能障碍是一个关键因素,影响细胞能量代谢、氧化应激和甾体激素生成。本研究探讨了月经血源性干细胞(MenSCs)及其外泌体在减轻 PCOS 颗粒细胞线粒体功能障碍和氧化应激中的治疗潜力。

方法

使用来曲唑诱导的 PCOS 大鼠模型,收获和培养颗粒细胞。使用 MenSCs 和它们的外泌体来评估它们对 PCOS 颗粒细胞中线粒体生物发生、氧化应激和雌激素产生的影响。

结果

结果显示,PCOS 颗粒细胞中线粒体生物发生减少,氧化应激增加,雌激素产生减少。MenSCs 和它们的外泌体治疗显著改善了 PCOS 颗粒细胞中的线粒体生物发生、氧化应激水平和雌激素产生。进一步的分析表明,MenSCs 比外泌体更有效,这归因于它们持续分泌的生物活性因子。机制上,MenSCs 和外泌体激活了与线粒体生物发生和抗氧化防御相关的途径,突出了它们在 PCOS 中的治疗潜力。

结论

本研究深入了解了颗粒细胞中线粒体在 PCOS 发病机制中的作用,并提出了 MenSCs 和外泌体作为减轻 PCOS 中线粒体功能障碍和氧化应激的潜在策略。需要进一步研究以了解潜在的机制并验证临床疗效,为解决 PCOS 的复杂性提供了有希望的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26a3/11330151/18534faf9e0e/13048_2024_1484_Fig1_HTML.jpg

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