Enhancement of mouse germ cell-associated genes expression by injection of human umbilical cord mesenchymal stem cells into the testis of chemical-induced azoospermic mice.
Various methods are currently under investigation to preserve fertility in males treated with high-dose chemotherapy and radiation for malignant and nonmalignant disorders. Human umbilical cord mesenchymal stem cells (HUC-MSCs), which possess potent immunosuppressive function and secrete various cytokines and growth factors, have the potential clinical applications. As a potential alternative, we investigate whether injection of HUC-MSCs into the interstitial compartment of the testes to promote spermatogenic regeneration efficiently. HUC-MSCs were isolated from different sources of umbilical cords and injected into the interstitial space of one testis from 10 busulfan-treated mice (saline and HEK293 cells injections were performed in a separate set of mice) and the other testis remained uninjected. Three weeks after MSCs injection, Relative quantitative reverse transcription polymerase chain reaction was used to identify the expression of 10 of germ cell associated, which are all related to meiosis, demonstrated higher levels of spermatogenic gene expression (2-8 fold) in HUC-MSCs injected testes compared to the contralateral uninjected testes (five mice). Protein levels for germ cell-specific genes, miwi, vasa and synaptonemal complex protein (Scp3) were also higher in MSC-treated testes compared to injected controls 3 weeks after treatment. However, no different expression was detected in saline water and HEK293 cells injection control group. We have demonstrated HUC-MSCs could affect mouse germ cell-specific genes expression. The results also provide a possibility that the transplanted HUC-MSCs may promote the recovery of spermatogenesis. This study provides further evidence for preclinical therapeutic effects of HUC-MSCs, and explores a new approach to the treatment of azoospermia.
Rui-Feng
RF
Yang
Tai-Hua
TH
Liu
Kai
K
Zhao
Center of Reproductive Medicine, Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology; Wuhan Tongji Reproductive Medicine Hospital, Wuhan, China.
Cheng-Liang
CL
Xiong
D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics; D053713:Azoospermia / Q000139:chemically induced / Q000628:therapy*; D018797:Cell Cycle Proteins; D053487:DEAD-box RNA Helicases / Q000235:genetics; D004268:DNA-Binding Proteins; D015870:Gene Expression; D057809:HEK293 Cells / Q000637:transplantation; D006801:Humans; D007267:Injections; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013091:Spermatogenesis / Q000235:genetics*; D013094:Spermatozoa / Q000378:metabolism; D013737:Testis; D059631:Wharton Jelly / Q000166:cytology
D060565:Argonaute Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C448522:Piwil1 protein, mouse; D012333:RNA, Messenger; C490062:Sycp3 protein, mouse; C090864:Ddx4 protein, mouse; D053487:DEAD-box RNA Helicases