Knockdown of the tetraspan protein epithelial membrane protein-2 inhibits implantation in the mouse.
The establishment of pregnancy requires a successful molecular interaction between the trophectoderm cells of the blastocyst stage embryo and the endometrial cells of the uterus. These interactions are complex and require synchronous development and coordinated endocrine, paracrine, and autocrine communication. In this study, we demonstrate that the tetraspan protein epithelial membrane protein-2 (EMP2) is involved in these molecular interactions during implantation. EMP2, which is highly expressed in the uterus, translocates from an intracellular location to the apical surface of the endometrial epithelium during the window of implantation and is expressed in decidualized stromal cells. We developed plasmid constructs that utilized either ribozyme-mediated or short hairpin RNA-mediated mechanisms to target endometrial EMP2 mRNA for destruction. These constructs were transfected into the mouse uterus on day 1 of pregnancy using the technique of in vivo reproductive tract gene transfer. Reduction in EMP2 expression by either method resulted in a significant decrease in the number of implantation sites in the treated uterine horns as compared to control horns. These studies indicate a previously unknown function of tetraspan proteins in implantation and could provide a molecular framework for the development of therapeutic modalities for both contraception and fertility.
Molecular Biology Institute, Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Madhuri
M
Wadehra
Molina
M
Dayal
Monica
M
Mainigi
Teri
T
Ord
Ramaswamy
R
Iyer
Jonathan
J
Braun
Carmen J
CJ
Williams
D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D010064:Embryo Implantation / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D016337:RNA, Catalytic / Q000235:genetics / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D059470:Tetraspanins; D014162:Transfection
C113388:Emp2 protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D016337:RNA, Catalytic; D012333:RNA, Messenger; C512650:TSPAN2 protein, human; D059470:Tetraspanins; C512651:Tspan2 protein, mouse; C421446:hammerhead ribozyme RZ3-BL2