Experimental Study Of Menstrual Blood Mesenchymal Stem Cells Improve Chemotherapy-induced Premature Ovarian Failure In Mice Via IGF-1/AKT/FOXO3a Signaling

Objective To investigate the effect and molecular mechanism of menstrual blood mesenchymal stem cells(MenSCs)transplantation on improving ovarian function in mice with premature ovarian failure(POF)induced by chemotherapy.Methods A total of 48 C57 BJ female mi ce 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 chemoth erapy.Ovarian function was observed by monitoring serum sex hormone levels,counting the number of superovulated mature eggs and measuring ovarian wet weight.The mRNA expression of growth factor receptor-binding protein 10(GRB10),insulinlike growth factor receptor(IGF-1R),protein kinase B(AKT),forkhead box O3(FOXO3a)in ovaries was detected by qRT-PCR.The protein expressions of GRB10,p-FOXO3 a,and p-AKT were detected with Western blotting and immunohistochemist ry.Results The concentrations 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),(24.60 � 10.24)PCS,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 grou p than in MenSCs group(P=0.023).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-FOXO3 a 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 � 0.05,0.64 � 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,activate IGF-1 signaling pathway,upregulate p-FOXO3 a expression,and thereby activates the development of primordial follicles and improves POF.