Therapeutic efficacy of endometrial stem cells and their exosomes on autoimmune premature ovarian failure in rats
Objective To observe the therapeutic effects of endometrial stem cells(EnSCs)and their exosomes on rats with autoimmune premature ovarian failure(POF).Methods EnSCs were isolated and cultured from menstrual cy-cle decidua in female health volunteers,and were separately cultured in exosome-free medium or exosome-free medium supplemented with 50 μmol/L metformin.Exosomes were extracted from the culture supernatant and identified,named EnSC-Exo and EnSCs-Met-Exo,respectively.Fifteen 4-week-old SD female rats with normal estrous cycles were randomly divided into the control group,POF group,POF-EnSCs group,POF-Exo group,and POF-Met-Exo group,with three rats in each group;the autoimmune POF rat models were established by intraperitoneal subcutaneous double-point injection of immunological reagents in all groups except the control group,and then intraperitoneal injections of normal saline,En-SCs,EnSCs-Exo,and EnSCs-Met-Exo were given,respectively.Serum estradiol(E2),follicle-stimulating hormone(FSH)levels in each group were detected by ELISA.The ovarian tissues of each group were collected,and we observed the appearance and calculated the ovarian volume.Pathological conditions were observed and the number of primordial,primary,secondary,and atretic follicles were recorded after HE staining.Results Compared with the control group,the serum E2 level,ovarian volume,and the numbers of primary and secondary follicles in the POF group significantly de-creased,while the serum FSH level and the number of atretic follicles significantly increased(all P<0.05).Compared with the POF model group,the serum FSH levels and the numbers of atretic follicles in the POF-EnSCs group,POF-Exo group,and POF-Met-Exo group significantly decreased,and the serum E2 level and the number of primary and secondary follicles in the POF-Met-Exo group increased(all P<0.05).There was no statistically significant difference in the number of primordial follicles among all groups(all P>0.05).The ovarian appearance and pathological results of the control group were normal;the ovaries of the POF group were congested,the surface was collapsed,the granular sensation was not obvi-ous,and they appeared atrophic,with ovarian tissue showing stromal fibrosis,twisted zona pellucida,and infiltration of granulosa cells and inflammatory cells;the ovarian appearance of the POF-EnSCs group,POF-Exo group,and POF-Met-Exo group rats was close to that of the control group,and the ovarian tissue inflammation and stromal fibrosis were alleviat-ed in comparison with those of the POF group.Conclusion Intraperitoneal injection of human EnSCs and their exosomes EnSCs-Exo and EnSCs-Met-Exo can alleviate pathological changes such as ovarian fibrosis and inflammation and promote follicular development in autoimmune POF rats,with EnSCs-Met-Exo having a better therapeutic effect.
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