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HucMSC-Derived Exosomes Mitigate the Age-Related Retardation of Fertility in Female Mice.
Molecular Therapy ( IF 12.1 ) Pub Date : 2020-02-07 , DOI: 10.1016/j.ymthe.2020.02.003 Weijie Yang 1 , Jing Zhang 2 , Boqun Xu 3 , Yuanlin He 2 , Wei Liu 2 , Jiazhao Li 2 , Songying Zhang 4 , Xiaona Lin 4 , Dongming Su 5 , Tinghe Wu 6 , Jing Li 2
Molecular Therapy ( IF 12.1 ) Pub Date : 2020-02-07 , DOI: 10.1016/j.ymthe.2020.02.003 Weijie Yang 1 , Jing Zhang 2 , Boqun Xu 3 , Yuanlin He 2 , Wei Liu 2 , Jiazhao Li 2 , Songying Zhang 4 , Xiaona Lin 4 , Dongming Su 5 , Tinghe Wu 6 , Jing Li 2
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In mammals, resting primordial follicles serve as the ovarian reserve. The decline in ovarian function with aging is characterized by a gradual decrease in both the quantity and quality of the oocytes residing within the primordial follicles. Many reports show that mesenchymal stem cells have the ability to recover ovarian function in premature ovarian insufficiency (POI) or natural aging animal models; however, the underlying mechanism remains unclear. In this study, using exosomes derived from human umbilical cord mesenchymal stem cells (HucMSC-exos), we found the specific accumulation of exosomes in primordial oocytes. The stimulating effects of exosomes on primordial follicles were manifested as the activation of the oocyte phosphatidylinositol 3-kinase (PI3K)/mTOR signaling pathway and the acceleration of follicular development after kidney capsule transplantation. Further analysis revealed the stimulatory effects of HucMSC-exos on primordial follicles were through carrying functional microRNAs, such as miR-146a-5p or miR-21-5p. In aged female mice, the intrabursal injection of HucMSC-exos demonstrated the recovery of decreased fertility with increased oocyte production and improved oocyte quality. Although assisted reproductive technologies have been widely used to treat infertility, their overall success rates remain low, especially for women in advanced maternal age. We propose HucMSC-exos as a new approach to mitigate the age-related retardation of fertility in women.
中文翻译：
HucMSC衍生的外来体减轻了雌性小鼠与年龄相关的生育迟缓。
在哺乳动物中，静止的原始卵泡可作为卵巢储备。卵巢功能随着衰老而下降的特征在于，位于原始卵泡内的卵母细胞的数量和质量逐渐下降。许多报告表明，间质干细胞具有在卵巢功能不全（POI）或自然衰老动物模型中恢复卵巢功能的能力。但是，其潜在机制仍不清楚。在这项研究中，使用源自人脐带间充质干细胞（HucMSC-exos）的外泌体，我们发现了外泌体在原始卵母细胞中的特异性积累。外泌体对原始卵泡的刺激作用表现为卵母细胞磷脂酰肌醇3-激酶（PI3K）/ mTOR信号通路的激活和肾囊移植后卵泡发育的加速。进一步的分析表明，HucMSC-exos对原始卵泡的刺激作用是通过携带功能性microRNA，例如miR-146a-5p或miR-21-5p。在老年雌性小鼠中，法氏囊内注射HucMSC-exos可以恢复生育力下降，卵母细胞产量增加和卵母细胞质量提高的现象。尽管辅助生殖技术已被广泛用于治疗不育症，但其总体成功率仍然很低，尤其是对于高龄产妇。
更新日期：2020-02-07
中文翻译：
HucMSC衍生的外来体减轻了雌性小鼠与年龄相关的生育迟缓。
在哺乳动物中，静止的原始卵泡可作为卵巢储备。卵巢功能随着衰老而下降的特征在于，位于原始卵泡内的卵母细胞的数量和质量逐渐下降。许多报告表明，间质干细胞具有在卵巢功能不全（POI）或自然衰老动物模型中恢复卵巢功能的能力。但是，其潜在机制仍不清楚。在这项研究中，使用源自人脐带间充质干细胞（HucMSC-exos）的外泌体，我们发现了外泌体在原始卵母细胞中的特异性积累。外泌体对原始卵泡的刺激作用表现为卵母细胞磷脂酰肌醇3-激酶（PI3K）/ mTOR信号通路的激活和肾囊移植后卵泡发育的加速。进一步的分析表明，HucMSC-exos对原始卵泡的刺激作用是通过携带功能性microRNA，例如miR-146a-5p或miR-21-5p。在老年雌性小鼠中，法氏囊内注射HucMSC-exos可以恢复生育力下降，卵母细胞产量增加和卵母细胞质量提高的现象。尽管辅助生殖技术已被广泛用于治疗不育症，但其总体成功率仍然很低，尤其是对于高龄产妇。
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