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

• 来源期刊: 亚洲男性学杂志（英文版）
• 年，卷（期）: 2020,（1）
• 页码范围: 79-87
• 页数: 9页
• 语种: 英文
• DOI: 10.4103/aja.aja_49_19

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 [Ptpn1 1] 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 PN 11-13.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.