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壳寡糖在调节卵巢生殖干细胞功能和恢复化疗小鼠卵巢功能中的作用。

The role of Chito-oligosaccharide in regulating ovarian germ stem cells function and restoring ovarian function in chemotherapy mice.

机构信息

Department of Obstetrics & Gynecology, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München, Munich, Germany.

出版信息

Reprod Biol Endocrinol. 2021 Jan 25;19(1):14. doi: 10.1186/s12958-021-00699-z.

Abstract

In recent years, the discovery of ovarian germ stem cells (OGSCs) has provided a new research direction for the treatment of female infertility. The ovarian microenvironment affects the proliferation and differentiation of OGSCs, and immune cells and related cytokines are important components of the microenvironment. However, whether improving the ovarian microenvironment can regulate the proliferation of OGSCs and remodel ovarian function has not been reported. In this study, we chelated chito-oligosaccharide (COS) with fluorescein isothiocyanate (FITC) to track the distribution of COS in the body. COS was given to mice through the best route of administration, and the changes in ovarian and immune function were detected using assays of organ index, follicle counting, serum estrogen (E) and anti-Mullerian hormone (AMH) levels, and the expression of IL-2 and TNF-α in the ovaries. We found that COS significantly increased the organ index of the ovary and immune organs, reduced the rate of follicular atresia, increased the levels of E and AMH hormones, and increased the protein expression of IL-2 and TNF-α in the ovary. Then, COS and OGSCs were co-cultured to observe the combination of COS and OGSCs, and measure the survival rate of OGSCs. With increasing time, the fluorescence intensity of cells gradually increased, and the cytokines IL-2 and TNF-α significantly promoted the proliferation of OGSCs. In conclusion, COS could significantly improve the ovarian and immune function of chemotherapy model mice, and improve the survival rate of OGSCs, which provided a preliminary blueprint for further exploring the mechanism of COS in protecting ovarian function.

摘要

近年来,卵巢生殖干细胞(OGSCs)的发现为治疗女性不孕提供了新的研究方向。卵巢微环境影响 OGSCs 的增殖和分化,免疫细胞和相关细胞因子是微环境的重要组成部分。然而,改善卵巢微环境是否能调节 OGSCs 的增殖并重塑卵巢功能尚未有报道。在本研究中,我们用异硫氰酸荧光素(FITC)将壳寡糖(COS)螯合,以追踪 COS 在体内的分布。通过最佳给药途径将 COS 给予小鼠,并通过检测器官指数、卵泡计数、血清雌激素(E)和抗苗勒管激素(AMH)水平以及卵巢中 IL-2 和 TNF-α的表达来检测卵巢和免疫功能的变化。我们发现,COS 显著增加了卵巢和免疫器官的器官指数,降低了卵泡闭锁率,增加了 E 和 AMH 激素水平,并增加了卵巢中 IL-2 和 TNF-α的蛋白表达。然后,将 COS 和 OGSCs 共培养以观察 COS 和 OGSCs 的结合,并测量 OGSCs 的存活率。随着时间的增加,细胞的荧光强度逐渐增加,细胞因子 IL-2 和 TNF-α显著促进了 OGSCs 的增殖。总之,COS 可显著改善化疗模型小鼠的卵巢和免疫功能,并提高 OGSCs 的存活率,为进一步探索 COS 保护卵巢功能的机制提供了初步蓝图。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ef/7830852/08856552858e/12958_2021_699_Fig1_HTML.jpg

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