Abstract
BackgroundFemale 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.MethodsWe 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.ResultsIn 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.ConclusionThe BMMSCs derived from juvenile macaques can reverse ovarian ageing in elderly macaques.
Highlights
As females age, both fertility and ovarian endocrine function naturally decline due to waning follicle numbers as well as ageing-related cellular dysfunction [1, 2]
The results showed that a small number of primary Bone marrow mesenchymal stem cells (BMMSCs) migrated out in a short spindle shape after 3–4 days, and a large number of suspended impurities were present in the supernatant (Fig. 2a)
Our results showed that Prog, Testo, PRL, and E2 were significantly increased after BMMSC treatment, while follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Müllerian hormone (AMH) were not significantly different before and after BMMSC treatment
Summary
Both fertility and ovarian endocrine function naturally decline due to waning follicle numbers as well as ageing-related cellular dysfunction [1, 2]. Societal changes and the increasing desire to preserve fertility have led to various treatment methods, including sex hormone replacement, cytokines, and traditional Chinese medicine (TCM) treatments, to treat ovarian ageing, which regulates fertility and endocrine secretion. The long-term use of hormone replacement therapy may cause breast cancer, thrombosis, and other diseases [3]. TCM treatment can partially improve ovarian function, but TCM drug compositions have not been fully elucidated, and there are many uncertain factors [5]. It is necessary to seek new and effective treatment methods. 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
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