Reproductive Medicine Center, First Affiliated Hospital of Soochow University, 899 Pinghai Rd, Suzhou, 215000, Jiangsu, China.
International Peace Maternity and Child Health Hospital of China Welfare Institute, Shanghai, 200030, China.
J Ovarian Res. 2024 Apr 4;17(1):75. doi: 10.1186/s13048-024-01390-8.
Umbilical cord-derived mesenchymal stem cell (UCMSC) transplantation has been deeply explored for premature ovarian insufficiency (POI) disease. However, the associated mechanism remains to be researched. To explore whether and how the microRNA 21 (miR-21) functions in POI mice with UCMSCs transplantation, the autoimmune-induced POI mice model was built up, transplanted with or without UCMSCs transfect with the LV-hsa-miR-21-5p/LV-hsa-miR-21-5p-inhibition, with the transfection efficiency analyzed by QRT-PCR. Mice hormone secretion and the anti-Zona pellucida antibody (AZPAb) levels were analyzed, the ovarian morphological changes and folliculogenesis were observed, and the ovarian apoptosis cells were detected to evaluate ovarian function. The expression and localization of the PTEN/Akt/FOXO3a signal pathway-related cytokines were analyzed in mice ovaries.Additionally, the spleen levels of CD8 + CD28-T cells were tested and qualified with its significant secretory factor, interleukin 10 (IL-10). We found that with the LV-hsa-miR-21-5p-inhibition-UCMSCs transplantation, the mice ovarian function can be hardly recovered than mice with LV-NC-UCMSCs transplantation, and the PTEN/Akt/FOXO3a signal pathway was activated. The expression levels of the CD8 + CD28-T cells were decreased, with the decreased levels of the IL-10 expression. In contrast, in mice with the LV-hsa-miR-21-5p-UCMSCs transplantation, the injured ovarian function can be reversed, and the PTEN/AKT/FOXO3a signal pathway was detected activated, with the increased levels of the CD8 + CD28-T cells, and the increased serum levels of IL-10. In conclusion, miR-21 improves the ovarian function recovery of POI mice with UCMSCs transplantation, and the mechanisms may be through suppressing the PTEN/AKT/FOXO3a signal pathway and up-regulating the circulating of the CD8 + CD28-T cells.
脐带间充质干细胞（UCMSC）移植已在卵巢早衰（POI）疾病中得到深入研究。然而，相关机制仍有待研究。为了探讨 miRNA-21（miR-21）在 UCMSC 移植的 POI 小鼠中是否以及如何发挥作用，构建了自身免疫诱导的 POI 小鼠模型，移植了转染或未转染 LV-hsa-miR-21-5p/LV-hsa-miR-21-5p 抑制物的 UCMSCs，通过 QRT-PCR 分析转染效率。分析了小鼠激素分泌和抗透明带抗体（AZPAb）水平，观察了卵巢形态变化和卵泡发生，并检测了卵巢凋亡细胞以评估卵巢功能。分析了小鼠卵巢中 PTEN/Akt/FOXO3a 信号通路相关细胞因子的表达和定位。此外，还检测了脾中 CD8+CD28-T 细胞的水平，并对其显著分泌因子白细胞介素 10（IL-10）进行了鉴定。我们发现，与 LV-hsa-miR-21-5p 抑制物-UCMSC 移植相比，LV-NC-UCMSC 移植的小鼠卵巢功能几乎无法恢复，PTEN/Akt/FOXO3a 信号通路被激活。CD8+CD28-T 细胞的表达水平降低，IL-10 的表达水平降低。相反，在接受 LV-hsa-miR-21-5p-UCMSC 移植的小鼠中，受损的卵巢功能可以逆转，PTEN/AKT/FOXO3a 信号通路被检测到激活，CD8+CD28-T 细胞水平升高，血清中 IL-10 水平升高。总之，miR-21 改善了 POI 小鼠的卵巢功能恢复，UCMSC 移植，其机制可能是通过抑制 PTEN/AKT/FOXO3a 信号通路和上调循环 CD8+CD28-T 细胞。
