Establishing a nonlethal and efficient mouse model of male gonadotoxicity by intraperitoneal busulfan injection  

作　　者：Yun Xie Cun-Can Deng Bin Ouyang Lin-Yan Lv Jia-Hui Yao Chi Zhang Hai-Cheng Chen Xiao-Yan Liang Xiang-Zhou Sun Chun-Hua Deng Gui-Hua Liu 

机构地区：[1]Department of Andrology,The First Affiliated Hospital,Sun Yat-sen University,Guangzhou 510000,China [2]Guangdong Provincial Key Laboratory of Orthopedics and Traumatology,Guangzhou 510000,China [3]Reproductive Centre,The Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou 510000,China [4]Gastrointestinal Diseases Research Institute of Guangdong Province,The Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou 510000,China [5]Department of Andrology,Guangzhou First People’s Hospital,School of Medicine,South China University of Technology,Guangzhou 510000,China

出　　处：《Asian Journal of Andrology》2020年第2期184-191,共8页亚洲男性学杂志（英文版）

基　　金：This study was supported by the National Natural Science Foundation of China(No.81571489,No.81671834,No.81671449 and No.81871110);the Frontier and Key Technology Innovation Special Foundation of Guangdong Province,China(No.2016B030230001);the Natural Science Foundation of Guangdong Province,China(No.2014A030310359,No.2016A030313229 and No.2015A030313013);the Science and Technology Planning Project of Guangdong Province,China(No.2016A020214004);the Health Care Collaborative Innovation Foundation Major Projects of Guangzhou City,Guangdong Province,China(No.201604020189);the Youth Teacher Training Project of Sun Yat-sen University(No.17ykpy68 and No.18ykpy09).

摘　　要：An ideal animal model of azoospermia would be a powerful tool for the evaluation of spermatogonial stem cell(SSC)transplantation.Busulfan has been commonly used to develop such a model,but 30%–87%of mice die when administered an intraperitoneal injection of 40 mg kg^?1.In the present study,hematoxylin and eosin staining,Western blot,immunofluorescence,and quantitative real-time polymerase chain reaction were used to test the effects of busulfan exposure in a mouse model that received two intraperitoneal injections of busulfan at a 3-h interval at different doses(20,30,and 40 mg kg^?1)on day 36 or a dose of 40 mg kg^?1 at different time points(0,9,18,27,36,and 63 days).The survival rate of the mice was 100%.When the mice were treated with 40 mg kg^?1 busulfan,dramatic SSC depletion occurred 18 days later and all of the germ cells were cleared by day 36.In addition,the gene expressions of glial cell line-derived neurotrophic factor(GDNF),fibroblast growth factor 2(FGF2),chemokine(C-X-C Motif)ligand 12(CXCL12),and colony-stimulating factor 1(CSF1)were moderately increased by day 36.A 63-day,long-term observation showed the rare restoration of endogenous germ cells in the testes,suggesting that the potential period for SSC transplantation was between day 36 and day 63.Our results demonstrate that the administration of two intraperitoneal injections of busulfan(40 mg kg^?1 in total)at a 3-h interval to mice provided a nonlethal and efficient method for recipient preparation in SSC transplantation and could improve treatments for infertility and the understanding of chemotherapy-induced gonadotoxicity.

关 键 词：AZOOSPERMIA BUSULFAN gonadotoxicity INFERTILITY RECIPIENT preparation spermatogonial stem cell 

分 类 号：R697[医药卫生—泌尿科学]