Department of Obstetrics and Gynecology, Guizhou Medical University, Guiyang, China.
Stem Cell Bank of Guizhou Province, Guizhou Health-Biotech Biotechnology Co., Ltd., Guiyang, China.
Front Endocrinol (Lausanne). 2023 Jul 26;14:1205901. doi: 10.3389/fendo.2023.1205901. eCollection 2023.
Premature ovarian insufficiency (POI) induced by chemotherapy is an intractable disorder with a considerable incidence that commonly results in insufficient fertility and concomitant complications in female patients. Due to limitations in the current progress in POI diagnosis and treatment, there is an urgent need to develop novel remedies to improve ovarian function and protect fertility. The ameliorative effect of human umbilical cord mesenchymal stem cells (hUCMSCs) and exosomes derived from them in POI treatment could be a new hope for patients. Herein, we identified exosomes from hUCMSCs (hUCMSC-Exos). Then, systematic infusion of hUCMSC-Exos was accomplished via tail intravenous injection to investigate the feasibility of the treatment of rats with chemotherapy-induced POI by intraperitoneal injection of cyclophosphamide (CTX) and busulfan (BUS). Ovarian functions in the indicated group were evaluated, including oestrous cycle, serum sex hormone levels, follicle counts, ovarian pathological changes, proliferation and apoptosis of granulosa cells (GCs), and reproductive ability testing. Furthermore, the potential influence of hUCMSC-Exos on ovarian tissues was illuminated by conducting RNA-seq and multifaceted bioinformatics analyses. POI rats with hUCMSC-Exos transplantation exhibited a decrease in follicle-stimulating hormone (FSH) and apoptosis of GCs but an increase in oestradiol (E2), anti-Müllerian hormone (AMH), and the number of ovarian follicles and foetuses in the uterus. And the immunomodulation- and cellular vitality-associated gene sets in rats had also undergone moderate changes. Our data indicated the feasibility of hUCMSC-Exos in improving ovarian function and protecting fertility in chemotherapy-induced POI rats. HUCMSC-Exos can improve the local microenvironment of ovarian tissue in POI rats by participating in immune regulation, cellular viability, inflammation regulation, fibrosis and metabolism, and other related signal pathways.
化疗引起的卵巢早衰（POI）是一种发病率相当高的难治性疾病，常导致女性患者生育能力不足和伴随的并发症。由于 POI 诊断和治疗的当前进展有限，因此迫切需要开发新的疗法来改善卵巢功能和保护生育能力。人脐带间充质干细胞（hUCMSCs）及其衍生的外泌体在 POI 治疗中的改善作用可能为患者带来新的希望。在此，我们鉴定了来自 hUCMSCs 的外泌体（hUCMSC-Exos）。然后，通过尾静脉注射进行 hUCMSC-Exos 的系统输注，以研究通过腹腔注射环磷酰胺（CTX）和白消安（BUS）对化疗诱导的 POI 大鼠进行治疗的可行性。评估了指定组的卵巢功能，包括发情周期、血清性激素水平、卵泡计数、卵巢病理变化、颗粒细胞（GCs）的增殖和凋亡以及生殖能力测试。此外，通过进行 RNA-seq 和多方面的生物信息学分析，阐明了 hUCMSC-Exos 对卵巢组织的潜在影响。接受 hUCMSC-Exos 移植的 POI 大鼠的卵泡刺激素（FSH）减少，GCs 凋亡，但雌二醇（E2）、抗苗勒管激素（AMH）和卵巢卵泡数量以及子宫内胎儿增加。并且大鼠的免疫调节和细胞活力相关基因集也发生了适度变化。我们的数据表明，hUCMSC-Exos 在改善化疗诱导的 POI 大鼠的卵巢功能和保护生育能力方面具有可行性。hUCMSC-Exos 通过参与免疫调节、细胞活力、炎症调节、纤维化和代谢以及其他相关信号通路，改善 POI 大鼠卵巢组织的局部微环境。
