Submitted to: Molecular Reproduction and Development
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/24/2005
Publication Date: 7/20/2006
Citation: Imakawa, K., Imai, M., Sakai, A., Suzuki, M., Nagaoka, K., Sakai, S., Lee, S.-R., Chang, K.-T., Echternkamp, S.E., Christenson, R.K. 2006. Regulation of conceptus adhesion by endometrial CXC chemokines during the implantation period in sheep. Molecular Reproduction and Development. 73(7):850-858. Interpretive Summary: Successful pregnancy in sheep requires that the embryo become attached to the lining of the uterus. The mechanisms of this attachment are not clearly defined. In this experiment, the role of CXC9, CXC10, and CXC11 in implantation, and their interaction with components of the matrix surrounding most cells, was studied. Increasing expression of all three CXC proteins was observed during early pregnancy. Of the matrix components tested, only fibronectin caused a significant increase in adhesion of trophoblast cells. The ability of trophoblast cells to adhere to fibronectin increased during early pregnancy. Inhibition of CXC proteins with specific antibodies to each protein decreased adhesion to fibronectin. These results suggest that the CXC proteins may play a role in the adhesion of the sheep embryo to the lining of the uterus during early pregnancy.
Technical Abstract: To gain a better understanding of biochemical mechanisms of conceptus adhesion to the maternal endometrium in ruminant ungulates, the present study was performed to clarify roles of chemokines and extracellular matrix (ECM) components in the regulation of ovine blastocyst attachment to the endometrium. In addition to the chemokine, interferon-gamma inducible protein 10 kDa (IP-10, CXCL10), the chemokine receptor, CXCR3, also recognizes two other chemokines; monokine induced by IFN-gamma (MIG, CXCL9) and IFN-inducible T cell alpha chemoattractant (I-TAC, CXCL11). Similar to CXCL10, CXCL9, and CXCL11 were expressed in the uterus during the peri-implantation period, and CXCL9 mRNA expression was stimulated in endometrial explants from day 14 cyclic ewes by the addition of IFN-tau or IFN-gamma. Without ECM components, conceptus cell adhesion was low on day 14 of gestation and exhibited a 2.5-fold increase on day 17; adhesiveness on day 20 was 1/10 of that on day 14. Among various ECM components examined, trophoblast adhesion was greatest when fibronectin was used. Although day 14 conceptuses did not show much adhesive activity to fibronectin, day 17 trophoblast, and day 20 chorionic membrane exhibited 2.3-fold and 50-fold increase, respectively, which was enhanced by treatment with CXCL9 or CXCL10. These results indicate that through endometrial fibronectin and chemokines, ovine conceptus cells gain the ability to attach to the endometrium during pre-implantation period; however, elucidation of molecular mechanisms by which the conceptus acquires the adhesive ability during this time period awaits further investigation.