In mammalians, when early embryo developed into the blastocyst stage, it required implantation into the endometrium bed for further development and viability, which was referred as the implantation process. Successful implantation requires synchronization between an implantation-competent blastocyst and a receptive uterus. The establishment of uterine receptivity was mainly under the influence of progesterone and estrogen through their respective receptors. In humans, about 75% of early pregnancy failure is considered to be due to implantation defects. However, the molecular network governing the receptivity establishment still remains obscured.
The research team led by Dr. Haibin Wang mainly utilizes the genetic mouse models to explore the physiological function of target molecule, and a recent research has proven that the protein tyrosine phosphatase Shp2 is indispensable for uterine receptivity establishment and thus the embryo implantation. Further mechanism studies reveal that nuclear Shp2, rather than cytosolic Shp2, promotes the ERα transcription activity to upregulate the stroma progesterone receptor expression. And this is achieved by enhancing the Src kinase mediated ERα tyrosine phosphorylation which facilitates ERα binding to Pgr promoter in an ERK-independent manner in peri-implantation uteri. Besides uncovering a novel regulatory mechanism of Shp2 in embryo implantation, this study also provides some clues for the research about the estrogen and progesterone action.
The corresponding authors are Haibin Wang (Medical College of Xiamen University), Zhongxian Lv (School of Pharmaceutical Sciences, Xiamen University) and Chao Wang (College of Biological Sciences, China Agricultural University). This work was supported by the National Natural Science Foundation (81130009, 81330017, and 81490744 to H.W.; 81601285 to S.K.; and 31471106 to S.Z.).
The study entitled “Nuclear Shp2 directs normal embryo implantation via facilitating the ERα tyrosine phosphorylation by the Src kinase” has been published in PNAS journal ahead of print on Apr 20, 2017.