Homeobox genes for embryo implantation: From mouse to human

The proper development of uterus to a state of receptivity and the attainment of implantation competency for blastocyst are 2 indispensable aspects for implantation,which is considered to be a critical event for successful pregnancy. Like many developmental processes, a large number of transcription factors, such as homeobox genes, have been shown to orchestrate this complicated but highly organized physiological process during implantation. In this review, we focus on progress in studies of the role of homeobox genes, especially the Hox and Msx gene families, during implantation, together with subsequent development of post-implantation uterus and related reproductive defects in both mouse models and humans, that have led to better understanding of how implantation is precisely regulated and provide new insights into infertility.

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

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.

Frontier Progress in the Establishment of Trophoblast Stem Cell and the Identification of New Cell Subtypes at the Maternal-Fetal Interface

Proper development of the human placenta is of vital importance for a successful pregnancy,and a series of pregnancy complications are considered originating from dysfunctional placentas.Like other organ system development,placentation requires large numbers of co-regulators,while the underlying molecular mechanisms orchestrating the placental formation and function are poorly understood.Although we have made many signs of progress in understanding the placental architectures and developments using mouse models,the species-specific differences impede our progress due to the lack of appropriate model systems.In the past few years,major progress has been made by the establishment of novel in-vitro self-renewing stem cell models,as well as identifying the full picture of the cellular organization of the maternal and fetal interface.Providing the tools for the investigation of placentation and reproductive-related regulation mechanism.In this review,we focus on the detailed progress of the human trophoblast stem cells culturing system,and the cellular and molecular terrain at the maternal-fetal interface,respectively,thus providing new insights into placental development.