Research On The Functions Of Shp2 In Spermatocyte Meiosis During Spermatogenesis

PTPN11(also known as Shp2)is a widely expressed nonreceptor tyrosine phosphatase which is an major regulator in the growth factor induced signaling pathway and involves in many celluar functions such as cell proliferation,differentiation and migration.Indeed,the germline mutations in the human PTPN11 gene,encoding Shp2,were linked to Noonan(NS)and LEOPARD syndromes which is infertile in most of the male patients and the exact physiological function of Shp2 in germ cell development is largely unknown.Here,we first portray the Shp2 expression pattern in early process of spermatogenesis which was abundant in the cytoplasm of spermatogonia,but was remarkably dropped and transferred into the nucleus of meiotic cells.This dynamically expression pattern implied the diversity and complexity of Shp2 role in spermatogenesis.We use Stra8-cre to conditional disruption of Shp2 in male mouse postnatal germ cells.After effective deletion,the first wave of spermatogenesis are severely impaired and great loss of germ cells emerged.Further analysis demonstrated that the efficiency of knockout system is become lower along with the mouse development and the subfertility phenotype is accused by the incomplete cre-mediated Shp2 ablation in adult KO mouse.Immunostanging analysis about testis tissue denoted that the meiosis is precocious initiated at postnatal 9day(PN9)but arrested at zygotene stage in Shp2 knockout mouse.The cell apoptosis of abnormal meiotic spermatocytes was raised at PN10.Moreover,We use QRT-PCR of primary separated germ cells and immunostanging analysis of testis tissue showed that Shp2 deletion destroy the balance between proliferation/differentiation in spermatogonia,also most of meiotic specific genes are prematurely expression in KO spermatogonia and then their expression could not reach the proper peak value in later spermatocytes.We use nuclear spread immunostiang showed that DSB is initiated but the central homologous recombination complex RAD51/DMC1 complex could not formation in Shp2 knockout spermatocytes.Also synapsis are also damaged in Shp2 deletion spermatocytes.Altogether,our results suggests that Shp2 play a critical role in proper meiotic initiation and meiotic process.