Home  |   Archive  |   Online Submission  |   News & Events  |   Subscribe  |   APFA  |   Society  |   Contact Us  |   中文版

Ahead of print
Authors' Accepted
Current Issue
Special Issues
Browse by Category

Manuscript Submission

Online Submission
Online Review
Instruction for Authors
Instruction for Reviewers
English Corner new!

About AJA

About AJA
Editorial Board
Contact Us

Resources & Services

Email alert

Download area

Copyright licence
EndNote style file
Manuscript word template
Guidance for AJA figures
    preparation (in English)

Guidance for AJA figures
    preparation (in Chinese)

Proof-reading for the

AJA Club (in English)
AJA Club (in Chinese)


Volume 23, Issue 4 (July 2021) 23, 386–391; 10.4103/aja.aja_98_20

Protective effect of bone marrow mesenchymal stem cell-derived exosomes against the reproductive toxicity of cyclophosphamide is associated with the p38MAPK/ERK and AKT signaling pathways

Xiao-Bin Guo, Jia-Wen Zhai, Hui Xia, Jian-Kun Yang, Jun-Hao Zhou, Wen-Bin Guo, Cheng Yang, Ming Xia, Kang-Yi Xue, Cun-Dong Liu, Qi-Zhao Zhou

Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China

Correspondence: Dr. CD Liu (cundongliu@163.com) or Dr. QZ Zhou (zhouqizhao19841224@163.com)

Date of Submission 28-Sep-2020 Date of Acceptance 25-Nov-2020 Date of Web Publication 05-Feb-2021


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.

Keywords: bone marrow mesenchymal stem cells; cyclophosphamide; exosomes; reproductive toxicity

Full Text | PDF |

Browse:  595
Copyright 1999-2017  Shanghai Materia Medica, Shanghai Jiao Tong University.  All rights reserved