Abstract
Many studies have shown that mesenchymal stem cells have the ability to restore function in models of premature ovarian insufficiency disease, but few studies have used stem cells in the treatment of ovarian physiologic aging (OPA). This experimental study was designed to determine whether human amniotic fluid mesenchymal stem cells (hAFMSCs) have the ability to recover ovarian vitality and to determine how they function in this process. Mice (12–14 months old) were used in this study, and young fertile female mice (3–5 months old) were the control group. Ovarian markers for four stages of folliculogenesis and DNA damage genes were tested by qPCR and western blot. hAFMSCs were used to treat an OPA mouse model, and the animals treated with hAFMSCs displayed better therapeutic activity in terms of the function of the mouse ovary, increasing follicle numbers and improving hormone levels. In addition, our results demonstrated that the marker expression level in ovarian granular cells from patients with OPA was elevated significantly after hAFMSC treatment. In addition, the proliferation activity was improved, and apoptosis was dramatically inhibited after hAFMSCs were cocultured with hGCs from OPA patients. Finally, in this study, hAFMSCs were shown to increase the mRNA and protein expression levels of ovarian markers at four stages of folliculogenesis and to inhibit the expression of DNA damage genes. These works have provided insight into the view that hAFMSCs play an integral role in resisting OPA. Moreover, our present study demonstrates that hAMSCs recover ovarian function in OPA by restoring the expression of DNA damage genes.
Highlights
Ovarian physiologic aging (OPA) is a worldwide reproductive health problem (White et al, 2012)
After ovaries of the OPA mice were injected with human amniotic fluid mesenchymal stem cells (hAFMSCs), hematoxylin and eosin (HE) staining was performed, and it was proved that hAFMSCs could remarkably restore the follicle number of primordial follicles, primary follicles, secondary follicles, and antral follicles to 66%, 65%, 68%, and 59%, respectively, at week 4 in comparison with the control group (Figures 2A–D)
To transition from bench to bedside, Human granulosa cells (hGCs) derived from OPA patients were cocultured with hAFMSCs
Summary
Ovarian physiologic aging (OPA) is a worldwide reproductive health problem (White et al, 2012). Menopause is an inevitable stage during ovarian aging (Herbert et al, 2015). The growing primordial follicle pool serves as the initial source of hAFMSCs Restore Ovarian Function developing follicles during stages of meiosis, but it mirrors the lifetime of ovaries in mice, suffering an inevitable decline with increasing age (Ding et al, 2018a). Human granulosa cells (hGCs) are a significant class of ovarian cells. They are situated outside of the zona pellucida in oocytes and are connected to oocytes via gap junctions (Ding et al, 2017). It has been speculated that abnormal folliculogenesis is probably due to increased apoptosis and decreased proliferation of granulosa cells (Ding et al, 2018c). The destiny of ovarian follicles might determine the equilibrium between cell survival and cell death signaling pathways in granulosa cells, which are regulated by many genes, such as FSHR, AMH, FOXL2, and CYP19A1 (Huang et al, 2018)
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