Prokineticin 2 overexpression induces spermatocyte apoptosis in varicocele in rats  

作　　者：Ying Li Ting Zhou Yu-Fang Su Zhi-Yong Hu Jia-Jing Wei Wei Wang Chun-Yan Liu Kai Zhao Hui-Ping Zhang 

机构地区：[1]Family Planning Research Institute/Reproductive Medicine Center,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China [2]Departm ent of Gynecology and Obstetrics,Union Hospital,Torigji Medical College,Huangzhong University of Science and Technology,Wuhan 430030,China

出　　处：《Asian Journal of Andrology》2020年第5期500-506,共7页亚洲男性学杂志（英文版）

基　　金：the National Natural Science Foundation of China(Grant No.81871148,No.81701539 and No.81571496).

摘　　要：Varicocele is one of the most important causes of male infertility,as this condition leads to a decline in sperm quality.It is generally believed that the presence of varicocele induces an increase in reactive oxygen species levels,leading to oxidative stress and sperm apoptosis;however,the specific pathogenic mechanisms affecting spermatogenesis remain elusive.Prokineticin 2(PK2),a secretory protein,is associated with multiple biological processes,including cell migration,proliferation,and apoptosis.In the testis,PK2 is expressed in spermatocytes under normal physiological conditions.To investigate the role of PK2 in varicocele,a rat varicocele model was established to locate and quantify the expression of PK2 and its receptor,prokineticin receptor 1(PKR1),by immunohistochemistry and quantitative real-time PCR assays(qPCR).Moreover,H2O2 was applied to mimic the oxidative stress state of varicocele through coculturing with a spermatocyte-derived cell line(GC-2)in vitro,and the apoptosis rate was detected by flow cytometry.Here,we illustrated that the expression levels of PK2 and PKR1 were upregulated in the spermatocytes of the rat model.Administration of H202 stimulated the overexpression of PK2 in GC-2.Transfection of recombinant pCMV-HA-PK2 into GC-2 cells promoted apoptosis by upregulating cleaved-caspase-3,caspase-8,and B cell lymphoma 2-associated X;downregulating B cell lymphoma 2;and promoting the accumulation of intracellular calcium.Overall,we revealed that the varicocele-induced oxidative stress stimulated the overexpression of PK2,leading to apoptosis of spermatocytes.Our study provides new insight into the mechanisms underlying oxidative stress-associated male infertility and suggests a novel therapeutic target for male infertility.

关 键 词：APOPTOSIS oxidative stress prokineticin 2 VARICOCELE 

分 类 号：R697.24[医药卫生—泌尿科学]