EF Derived from Human Placental Mesenchymal Stem Cells Improves Premature Ovarian Insufficiency Via NRF2/HO-1 Activation
39 Pages Posted: 16 Jan 2019More...
Human placental mesenchymal stem cells (hPMSCs) are a potential therapeutic option for clinical applications because of their ability to produce cytokines and their capacity for trilineage differentiation. To date, few researchers have investigated the relevance of hPMSCs in the treatment with premature ovarian insufficiency (POI) at the oxidative stress level. A POI mouse model and human ovarian granule cells (hGCs) collected from individuals with POI were prepared to assess the therapeutic effects and illuminate the mechanism of hPMSCs in curing POI. Our results showed that hPMSCs displayed therapeutic activity on ovarian function in the POI mouse model, including recovered follicular numbers and increased marker expression. Furthermore, the yields of hPMSC-secreted EGF (epidermal growth factor) were higher than those of other growth factors. FACS and Western blot showed that EGF promoted the proliferation rate and inhibited the apoptosis rate in hGCs. FACS and ELISA indicated that the hPMSCs and EGF inhibited oxidative stress. In addition, protein assays demonstrated that EGF suppressed oxidative stress by dose-dependently upregulating the expression of the NRF2/HO-1 pathway and inhibited the apoptosis rate by regulating the PTEN/PI3K/AKT pathway. These findings demonstrate for the first time the molecular cascade and related cell biology events involved in the mechanism by which EGF derived from hPMSCs improves ovarian function during POI via the reduction of oxidative stress by activating the NRF2/HO-1 signaling pathway.
Funding Statement: This work was supported by the grants from National Natural Science Foundation of China (81801515, 81801494), Suzhou science and technology for people's livelihood (SYS2018081), Suzhou introduce expert team of clinical medicine (SZYJTD201708).
Declaration of Interests: The authors declare no conflicts of interest.
Ethics Approval Statement: The study protocol was approved by the Ethics Committee for Clinical Research at the Suzhou Hospital affiliated with Nanjing Medical University.
Keywords: Human placental mesenchymal stem cells; premature ovarian insufficiency; epidermal growth factor; Oxidative stress; NRF2/HO-1
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