Spermatogenic dysfunction caused by cyclophosphamide(CP)chemotherapy has seriously influenced the life quality of patients.Unfortunately,treatments for CP-induced testicular spermatogenic dysfunction are limited,and t...Spermatogenic dysfunction caused by cyclophosphamide(CP)chemotherapy has seriously influenced the life quality of patients.Unfortunately,treatments for CP-induced testicular spermatogenic dysfunction are limited,and the molecular mechanisms are not fully understood.For the first time,here,we explored the effects of bone marrow mesenchymal stem cell-derived exosomes(BMSC-exos)on CP-induced testicular spermatogenic dysfunction in vitro and in vivo.BMSC-exos could be taken up by spermatogonia(GC1-spg cells).CP-injured GC1-spg cells and BMSC-exos were cocultured at various doses,and then,cell proliferation was measured using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide(MTT)assay.In addition,photophosphorylation of extracellular-regulated kinase(ERK),p38 mitogen-activated protein kinase(p38MAPK),and protein kinase B(AKT)proteins was evaluated by western blotting as well as apoptosis in GC1-spg cells measured using flow cytometry.Treatment with BMSC-exos enhanced cell proliferation and reduced apoptosis of CP-injured GCI-spg cells.Phosphorylated levels of ERK,AKT,and p38MAPK proteins were reduced in CP-injured spermatogonia when co-treated with BMSC-exos,indicating that BMSC-exos acted against the reproductive toxicity of CP via the p38MAPK/ERK and AKT signaling pathways.In experiments in vivo,CP-treated rats received BMSC-exos by injection into the tail vein,and testis morphology was compared between treated and control groups.Histology showed that transfusion of BMSC-exos inhibited the pathological changes in CP-injured testes.Thus,BMSC-exos could counteract the reproductive toxicity of CP via the p38MAPK/ERK and AKT signaling pathways.The findings provide a potential treatment for CP-induced male spermatogenic dysfunction using BMSC-exos.展开更多
基金This study was supported by grants from the National Natural Science Foundation of China(No.81772257)the Guangdong Provincial Natural Science Foundation of China(No.2018A030313697).
文摘Spermatogenic dysfunction caused by cyclophosphamide(CP)chemotherapy has seriously influenced the life quality of patients.Unfortunately,treatments for CP-induced testicular spermatogenic dysfunction are limited,and the molecular mechanisms are not fully understood.For the first time,here,we explored the effects of bone marrow mesenchymal stem cell-derived exosomes(BMSC-exos)on CP-induced testicular spermatogenic dysfunction in vitro and in vivo.BMSC-exos could be taken up by spermatogonia(GC1-spg cells).CP-injured GC1-spg cells and BMSC-exos were cocultured at various doses,and then,cell proliferation was measured using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide(MTT)assay.In addition,photophosphorylation of extracellular-regulated kinase(ERK),p38 mitogen-activated protein kinase(p38MAPK),and protein kinase B(AKT)proteins was evaluated by western blotting as well as apoptosis in GC1-spg cells measured using flow cytometry.Treatment with BMSC-exos enhanced cell proliferation and reduced apoptosis of CP-injured GCI-spg cells.Phosphorylated levels of ERK,AKT,and p38MAPK proteins were reduced in CP-injured spermatogonia when co-treated with BMSC-exos,indicating that BMSC-exos acted against the reproductive toxicity of CP via the p38MAPK/ERK and AKT signaling pathways.In experiments in vivo,CP-treated rats received BMSC-exos by injection into the tail vein,and testis morphology was compared between treated and control groups.Histology showed that transfusion of BMSC-exos inhibited the pathological changes in CP-injured testes.Thus,BMSC-exos could counteract the reproductive toxicity of CP via the p38MAPK/ERK and AKT signaling pathways.The findings provide a potential treatment for CP-induced male spermatogenic dysfunction using BMSC-exos.