Newly identified endometrial genes of importance for implantation.
The mammalian uterus is normally not receptive to embryo implantation except during the very limited 'window of implantation'. To identify genes that may be responsible for this phenomenon the technique of RNA differential display (DD-PCR) was applied to implantation and inter-implantation sites on day 4.5 of pregnancy in the mouse, the time at which the blastocyst becomes attached to the endometrium. Three of these genes were identified as splicing factor SC35, calbindin-D9k and monoclonal non-specific suppressor factor beta (MNSFbeta). Expression of SC35 mRNA, which is responsible for removal of introns from pre-mRNA, is much higher in implantation than in interimplantation sites during pregnancy. Expression of alternatively spliced mRNAs for SC35 is differentially regulated by early pregnancy and steroid hormones. By contrast, calbindin-D9k, a regulator of calcium, is upregulated by progesterone and its mRNA increases in the uterus during early pregnancy compared with during the cycle, although it is significantly lower in implantation sites than in interimplantation sites on days 4.5-5.5 of pregnancy, but subsequently becomes barely detectable in both sites. The mRNA for calbindin-D9k is predominantly in endometrial luminal epithelium. MNSFbeta, a cytokine involved in regulation of the immune system, showed lower expression at implantation sites than interimplantation sites on day 4.5 of pregnancy, when embryos first attach to the uterus and initiate implantation, and on day 5.5 when implantation has advanced. Immunohistochemically, the protein was localized to endometrial stromal cells in the non-pregnant uterus, but disappeared as decidualization progressed. The precise roles of these three proteins in the process of embryo implantation remains to be determined. Homologues of the proteins may contribute to the development of the 'window of implantation' in the human and hence be appropriate targets for new post-coital contraceptives or may be manipulated to improve fertility.
Salamonsen
Lois A
LA
Prince Henry's Institute of Medical Research, PO Box 5152, Clayton, Vic. 3168, Australia. lois.salamonsen@med.monash.edu.au
Nie
Guiying
G
Findlay
Jock K
JK
D000818:Animals; D064026:Calbindins; D010064:Embryo Implantation / Q000235:genetics*; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins; D064030:S100 Calcium Binding Protein G / Q000235:genetics; D000068103:Serine-Arginine Splicing Factors; D013491:Suppressor Factors, Immunologic / Q000235:genetics
D064026:Calbindins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D064030:S100 Calcium Binding Protein G; C576506:S100G protein, human; C576507:S100g protein, mouse; C499372:SRSF2 protein, mouse; D013491:Suppressor Factors, Immunologic; C072169:monoclonal nonspecific suppressor factor; D000068103:Serine-Arginine Splicing Factors