Female sex hormone secretion and reproductive ability decrease with ageing. Bone marrow mesenchymal stem cells (BMMSCs) have been postulated to play a key role in treating ovarian ageing. We used macaque ovarian ageing models to observe the structural and functional changes after juvenile BMMSC treatment. Moreover, RNA-seq was used to analyse the ovarian transcriptional expression profile and key pathways through which BMMSCs reverse ovarian ageing. In the elderly macaque models, the ovaries were atrophied, the regulation ability of sex hormones was reduced, the ovarian structure was destroyed, and only local atretic follicles were observed, in contrast with young rhesus monkeys. Intravenous infusion of BMMSCs in elderly macaques increased ovarian volume, strengthened the regulation ability of sex hormones, reduced the degree of pulmonary fibrosis, inhibited apoptosis, increased density of blood vessels, and promoted follicular regeneration. In addition, the ovarian expression characteristics of ageing-related genes of the elderly treatment group reverted to that of the young control group, 1258 genes that were differentially expressed, among which 415 genes upregulated with age were downregulated, 843 genes downregulated with age were upregulated after BMMSC treatment, and the top 20 differentially expressed genes (DEGs) in the protein-protein interaction (PPI) network were significantly enriched in oocyte meiosis and progesterone-mediated oocyte maturation pathways. The BMMSCs derived from juvenile macaques can reverse ovarian ageing in elderly macaques.

中文翻译：

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来自幼年猕猴的骨髓间充质干细胞逆转了老年猕猴的卵巢衰老

女性性激素分泌和生殖能力随着年龄的增长而下降。骨髓间充质干细胞（BMMSC）被认为在治疗卵巢衰老中发挥着关键作用。我们利用猕猴卵巢衰老模型来观察幼年BMMSC治疗后结构和功能的变化。此外，RNA-seq用于分析卵巢转录表达谱和BMMSC逆转卵巢衰老的关键途径。老年猕猴模型与年轻恒河猴相比，卵巢萎缩，性激素调节能力降低，卵巢结构被破坏，仅观察到局部闭锁卵泡。老年猕猴静脉输注BMMSCs可增加卵巢体积，增强性激素调节能力，减轻肺纤维化程度，抑制细胞凋亡，增加血管密度，促进卵泡再生。此外，老年治疗组卵巢衰老相关基因的表达特征恢复至年轻对照组，有1258个差异表达基因，其中415个随年龄上调的基因下调，843个随年龄下调的基因上调。 BMMSC处理后，蛋白质-蛋白质相互作用（PPI）网络中前20个差异表达基因（DEG）在卵母细胞减数分裂和孕酮介导的卵母细胞成熟途径中显着富集。来自幼年猕猴的骨髓间充质干细胞可以逆转老年猕猴的卵巢衰老。