Screening And Identification Of The Gene. Human Endometrial Receptivity

ObjectiveIn vitro fertilization-embryo transfer(IVF-ET)has been employed in treating infertility for about 30 years.Despite the more stable techniques in lab and the increased number of high-quality embryos,implantation rate is still around 20%.The receptivity of endometrium may be the main hinder.Appearance and disappearance of implantation window depend on expression of a specific set of genes in endometrium. Morphological finding showed 1-2 days difference of the implantation window in the controlled ovarian hyperstimulation(COH)cycle comparing to the natural cycle,and that some genes have been detected relating to embryo adhesion and invasion. However,there is no gene which can decide the endometrial receptivity all by itself. In this study scanning the complete genome array of endometrium at the luteal phase of COH cycle and the natural cycle was conducted to find the gene expression of implantation window with the aim to know more about genes associated with endometrial receptivity.MethodsFive endometrial samples from days of LH+4,LH+7 and HCG+7 were taken into HU133 plus2.0 microarray scanning.These 5 samples and the other 7 samples from day of LH+7 and 8 samples from HCG+7 received Real-time PCR quantitation(QPCR)test.All samples were certainly matched with their stages of pathohistology.Based on the results of microarray scanning,we selected S100P which was suspected to be a new implantation associated gene for further research by immunofluorence,RT-PCR and western-blot analysis.ResultsComparing the complete genome expression spectra of LH+7 to that of LH+4,581 genes have expression differences,among which 395 were up-regulation genes and 186 were down-regulation genes.When it went to HCG+7 and LH+7,320 genes have expression differences,among which 145 genes were down-regulated,and 175 genes were up-regulated.In the QPCR test,some up-regulation gene's expression was much lower on the day HCG+7 than LH+7,such as PAEP,S100P,SOD and GDF15.The results demonstrated that S100P which was low in proliferative phase and early secrectory phase,elevated significantly in implantantion window(LH+7). The other three S100 family members S100A4,S100A13 and S100A6,was not comparable with S100P expression during the menstrual cycle.ConclusionsMicroarray scanning provides a global gene expression spectrum of different phase of human endometrium.A set of genes,such as PAEP,S100P,SOD and GDF15, express high at the implantation window phase of the endometrium,but not show adequate expression after controlled ovarian hyperstimulation;From the hierarchical clustering the characters of endometrium at LH+4 are in great resemblance with the characters of endometrium at LH+2.This may hint that gene expression changes at implantation window proceed quickly within 1 or 2 days,and that there may exist a "trigger effect" for the opening of implantation window.The S100P gene which has not been described before expressed especially high in implantation window. Therefore S100P may be a new gene associated with endometrial receptivity.