Human umbilical cord mesenchymal stem cells restore chemotherapy-induced premature ovarian failure by inhibiting ferroptosis in vitro ovarian culture system.

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Jiaqi Chen, Zhuoying He, Wenjuan Xu, Yumiao Kang, Fengyu Zhu, Heng Tang, Jianye Wang, Fei Zhong
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引用次数: 0

Abstract

Background: Mesenchymal stem cells (MSCs) have shown potential in repairing chemotherapy-induced premature ovarian failure (POF). However, challenges such as stem cell loss and immune phagocytosis post-transplantation hinder their application. Due to easy and safe handling, in vitro ovarian culture is widely available for drug screening, pathophysiological research, and in vitro fertilization. MSCs could exhibit therapeutic capacity for ovarian injury, and avoid stem cell loss and immune phagocytosis in vitro tissue culture system. Therefore, this study utilizes an in vitro ovarian culture system to investigate the reparative potential of human umbilical cord mesenchymal stem cells (hUCMSCs) and their mechanism.

Methods: In this study, a chemotherapy-induced POF model was established by introducing cisplatin in vitro ovarian culture system. The reparative effects of hUCMSCs on damaged ovarian tissue were validated through Transwell chambers. Tissue histology examination, immunohistochemical staining, Western blotting, and RT-PCR were employed to evaluate the expression effects of hUCMSCs on ferroptosis and fibrosis-related genes during the process of repairing cisplatin-induced POF.

Results: Cisplatin was found to activate ovarian follicles in vitro POF model. Transcriptomic sequencing analysis revealed that cisplatin could activate genes associated with ferroptosis. hUCMSCs alleviated cisplatin-induced POF by suppressing the expression of ferroptosis. Moreover, inhibiting ferroptosis by hUCMSCs also ameliorated ovarian hormone levels and reduced the expression of fibrosis-related factors α-SMA and COL-I in the ovaries.

Conclusions: This study confirms that cisplatin-induced ovarian damage via ferroptosis in vitro POF model, and hUCMSCs repair ovarian injury by inhibiting the ferroptosis pathway and suppressing fibrosis. This research contributes to evaluating the effectiveness of hUCMSCs in treating chemotherapy-induced POF by inhibiting ferroptosis in an in vitro ovarian culture system and provides a potential therapeutic strategy for chemotherapy-induced POF.

人脐带间充质干细胞通过抑制体外卵巢培养系统中的铁变态反应,恢复化疗引起的卵巢早衰。
背景:间充质干细胞(MSCs)已显示出修复化疗引起的卵巢早衰(POF)的潜力。然而,移植后干细胞丢失和免疫吞噬等挑战阻碍了它们的应用。由于操作简便、安全,体外卵巢培养可广泛用于药物筛选、病理生理学研究和体外受精。间充质干细胞可显示出对卵巢损伤的治疗能力,并在体外组织培养系统中避免干细胞损失和免疫吞噬。因此,本研究利用体外卵巢培养系统研究人脐带间充质干细胞(hUCMSCs)的修复潜力及其机制:本研究通过在体外卵巢培养系统中引入顺铂,建立了化疗诱导的 POF 模型。通过 Transwell 细胞室验证了 hUCMSCs 对受损卵巢组织的修复作用。采用组织学检查、免疫组化染色、Western 印迹和 RT-PCR 等方法,评估 hUCMSCs 在顺铂诱导的 POF 修复过程中对铁变态反应和纤维化相关基因的表达影响:结果:在体外 POF 模型中,顺铂可激活卵巢滤泡。转录组测序分析表明,顺铂可激活与铁突变相关的基因。hUCMSCs 可通过抑制铁突变的表达来缓解顺铂诱导的 POF。此外,通过 hUCMSCs 抑制铁突变还能改善卵巢激素水平,减少卵巢纤维化相关因子 α-SMA 和 COL-I 的表达:本研究证实,在体外 POF 模型中,顺铂通过铁蛋白沉积诱导卵巢损伤,而 hUCMSCs 可通过抑制铁蛋白沉积途径和抑制纤维化来修复卵巢损伤。这项研究有助于评估 hUCMSCs 在体外卵巢培养系统中通过抑制铁凋亡治疗化疗诱导的 POF 的有效性,并为化疗诱导的 POF 提供了一种潜在的治疗策略。
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
Reproductive Biology and Endocrinology
Reproductive Biology and Endocrinology 医学-内分泌学与代谢
CiteScore
7.90
自引率
2.30%
发文量
161
审稿时长
4-8 weeks
期刊介绍: Reproductive Biology and Endocrinology publishes and disseminates high-quality results from excellent research in the reproductive sciences. The journal publishes on topics covering gametogenesis, fertilization, early embryonic development, embryo-uterus interaction, reproductive development, pregnancy, uterine biology, endocrinology of reproduction, control of reproduction, reproductive immunology, neuroendocrinology, and veterinary and human reproductive medicine, including all vertebrate species.
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