Journal of Shandong University (Health Sciences) ›› 2020, Vol. 58 ›› Issue (2): 13-20.doi: 10.6040/j.issn.1671-7554.0.2019.1278

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Menstrual blood mesenchymal stem cells improve premature ovarian failure in mice via IGF-1 signaling

XU Yanyan1,2, YAN Bei2,3, WANG Rui2, WANG Hongyan1,3   

  1. 1. Department of Human Anatomy and Histology and Embryology, Ningxia Medical University, Yinchuan 750004, Ningxia, China;
    2. Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Ningxia Medical University, Yinchuan 750004, Ningxia, China;
    3. Sperm Bank of General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, China
  • Online:2020-02-10 Published:2022-09-27

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Abstract: Objective To investigate the effect and molecular mechanism of menstrual blood mesenchymal stem cells(MenSCs)transplantation on the ovarian function in mice with premature ovarian failure(POF)induced by chemotherapy. Methods A total of 48 C57BJ female mice were randomly divided into control, POF and MenSCs groups. The POF models were induced by intraperitoneal injection of cyclophosphamide combined with busulfan, and the MenSCs models were established by injecting MenSCs via tail vein 3 days after chemotherapy. The mRNA expression of growth factor receptor-binding protein 10(GRB10)in ovaries was detected with qRT-PCR. The protein expressions of GRB10, forkhead box O3(FOXO3a), p-FOXO3a, insulin-like growth factor receptor(IGF-1R), p-IGF-1R, protein kinase B(AKT)and p-AKT were detected with Western blotting. Results The concentration of serum estradiol in the control group, POF group, and MenSCs group was(222.29±35.13),(90.87±28.76), and(193.24±48.74)pg/mL, respectively(F=19.332, P<0.001), and it was lower in POF group than in control group(P<0.001)and MenSCs group(P<0.001). The number of superovulated mature eggs was 40.00±10.07, 9.00±7.42, and 24.60±10.24, respectively(F=13.792, P=0.001), and it was higher in control group(P<0.001)and MenSCs group(P=0.021)than in POF group, and higher in control group than in MenSCs group(P=0.039). The gray value of GRB10 protein bands was 1.22±0.05, 1.82±0.13, and 1.10±0.09, respectively (F=94.340, P<0.001), and it was higher in POF group than in control group(P<0.001)and MenSCs group(P<0.001). The gray value of p-FOXO3a protein bands was 0.80±0.08, 0.33±0.06, and 0.76±0.05, respectively(F=98.673, P<0.001), and it was lower in POF group than in control group(P<0.001)and MenSCs group(P<0.001). The gray value of p-IGF-1R protein bands was 0.31±0.10, 0.32±0.08, and 0.42±0.01, respectively(F=3.882, P=0.044), and it was higher in MenSCs group than in control group(P=0.023)and POF group(P=0.039). The gray value of p-AKT protein bands was 0.57±0.02, 0.51±0.05, and 0.64±0.03, respectively(F=22.227, P<0.001), and it was higher in MenSCs group than in control group(P=0.005)and POF group(P<0.001), and higher in control group than in POF group(P=0.004). Conclusion Via the binding of IGF-1 and IGF-1R, MenSCs transplantation may upregulate p-IGF-1R expression while downregulate GRB10 expression, activate IGF-1 signaling pathway, upregulate p-FOXO3a expression, and thereby activates the development of primordial follicles and improves POF.

Key words: Menstrual blood mesenchymal stem cells, Premature ovarian failure, Growth factor receptor-binding protein 10, Insulin-like growth factor 1, Forkhead box O3

CLC Number: 

  • R711.75
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