The role of tyrosine phosphatase Shp2 in spermatogonial differentiation and spermatocyte meiosis  

作　　者：Yang Li Wen-Sheng Liu Jia Yi Shuang-Bo Kong Jian-Cheng Ding Yi-Nan Zhao Ying-Pu Tian Gen-Sheng Feng Chao-Jun Li Wen Liu Hai-Bin Wang Zhong-Xian Lu 

机构地区：[1]School of Pharmaceutical Sciences,State Key Laboratory of Cellular Stress Biology,Xiamen University,Xiamen 361005,China [2]Fujian Provincial Key Laboratory of Reproductive Health Research,Medical College of Xiamen University,Xiamen 361005,China [3]Fujian Provincial Key Laboratory of Innovative Drug Target Research,School of Pharmaceutical Sciences,Xiamen 361005,China [4]Department of Pathology,Division of Biological Sciences,University of California at San Diego,La Jolla,CA 92093,USA [5]Ministry of Education Key Laboratory of Model Animals for Disease Study,Model Animal Research Center and Medical School of Nanjing University,National Resource Center for Mutant Mice,Nanjing 210061,China

出　　处：《Asian Journal of Andrology》2020年第1期79-87,共9页亚洲男性学杂志（英文版）

基　　金：This work was supported by the National Key R&D Program of China(No.2018YFC1003701 and No.2017YFC1001402);the National Natural Science Foundation of China(Grant No.31171375).

摘　　要：The transition from spermatogonia to spermatocytes and the initiation of meiosis are key steps in spermatogenesis and are precisely regulated by a plethora of proteins.However,the underlying molecular mechanism remains largely unknown.Here,we report that Src homology domain tyrosine phosphatase 2(Shp2;encoded by the protein tyrosine phosphatase,nonreceptor type 11[Ptpn11]gene)is abundant in spermatogonia but markedly decreases in meiotic spermatocytes.Conditional knockout of Shp2 in spermatogonia in mice using stimulated by retinoic acid gene 8(Stra8)-cre enhanced spermatogonial differentiation and disturbed the meiotic process.Depletion of Shp2 in spermatogonia caused many meiotic spermatocytes to die;moreover,the surviving spermatocytes reached the leptotene stage early at postnatal day 9(PN9)and the pachytene stage at PN11-13.In preleptotene spermatocytes,Shp2 deletion disrupted the expression of meiotic genes,such as disrupted meiotic cDNA 1(Dmc1),DNA repair recombinase rad51(Rad51),and structural maintenance of chromosome 3(Smc3),and these deficiencies interrupted spermatocyte meiosis.In GC-1 cells cultured in vitro,Shp2 knockdown suppressed the retinoic acid(RA)-induced phosphorylation of extracellular-regulated protein kinase(Erk)and protein kinase B(Akt/PKB)and the expression of target genes such as synaptonemal complex protein 3(Sycp3)and Dmc1.Together,these data suggest that Shp2 plays a crucial role in spermatogenesis by governing the transition from spermatogonia to spermatocytes and by mediating meiotic progression through regulating gene transcription,thus providing a potential treatment target for male infertility.

关 键 词：cell DIFFERENTIATION gene expression SPERMATOGENESIS TRANSGENIC MOUSE 

分 类 号：R697[医药卫生—泌尿科学]