| Objective: Patients who suffer from premature ovarian insufficiency(POI)are characterized by abnormal menstruation with hormonal disorders in woman younger than40 years whereas certain etiological and pathophysiological mechanisms have not been clearly defined.Recently,a non-invasive and abundant source of Men SCs lends significant therapeutic promise in restoration of female reproductive system damage.This report describes experiments designed to determine whether Men SCs were effective in POI.Methods: Animals were divided into three groups in total of 150 female mice(No group without treatment as blank control,Mo group with cyclophosphamide(CTX)injection and Me group preconditioned with CTX followed by cells graft).CTX intraperitoneal injection was performed to establish POI models.Men SCs were grafted on the seventh day.After treatment,blood samples,ovaries and uterus were collected for further evaluation of this study.During the study,ovarian follicles were counted and classified.Estrous cycles and live births were recorded.Additionally,ovarian function was evaluated by serum hormones and apoptosis in ovaries.Results: In our present study,our findings demonstrated that Men SCs presented a low expression of hematopoietic cells antigens but a high expression of classical mesenchymal stem cells surface markers.Men SCs could be induced into adipogenic,chondrogenic and osteogenic differentiation.In vivo,ovarian weight increased after cells therapy.Furthermore,pathological analysis revealed that CTX could lead to disturbance in follicles development in both quantity and quality while Men SCs transplantation could restore the follicle injury partially.In addition,estrous cycles of mice in Mo group were prone to be arrested on diestrus when compared with No group,but this situation could be relieved in part after treatment of Men SCs.Serum sample were obtained of each mouse,ELISA results indicated a positive effect of Men SCs transplantation when the homeostasis of hormones in vivo was broken by CTX.Data statistics revealed less live births after CTX treatment than No group and Me group with statistical significance.For further comparison of ovarian function among these groups,TUNEL assay was carried out to determined apoptotic cells in ovarian tissues.Results brought up such a hint that there were fairly more apoptotic cells existing in Mo group than No group and Men SCs could dramatically reduce the occurrence of apoptosis.Conclusion: The efficacy of Men SCs in the treatment of POI lends considerable therapeutic potential with great advantages of non-invasiveness,robust source and low immunogenicity,over other sources of MSCs.Additionally,our study focuses on the reparative effects of Men SCs on POI mouse models,yet it is still not known whether our results are applicable to further studies in other higher mammals or even human beings.It should be pointed out in particular that POI patients are usually amenorrheic clinically and it is hard for them to collect menstrual blood from normally spontaneous menstruation.In these patients,artificial menstrual cycles are often adopted to sustain normal function of their uteri and thus they regain menstruation.However,whether can Men SCs from normal woman or POI patients exhibit same effect is still unknown and it is in urgent need of more researches in POI treatment to compare the similarities and differences of Men SCs between normal donors and POI patients.Apart from this,it is necessary to explore the tumorigenicity of Men SCs transplantation in vivo with follow-up for long time to comprehensively assess the safety of this treatment.Certainly,Men SCs therapy has a great potential in the future. |
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