Submitted to: Biology of Reproduction
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/30/2002
Publication Date: 4/1/2003
Citation: NAGAOKA, K., SAKAI, A., NOJIMA, H., SUDA, Y., YOKOMIZO, Y., IMAKAWA, K., SAKAI, S., CHRISTENSON, R.K. A CHEMOKINE, INTERFERON (IFN)-GAMMA-INDUCIBLE PROTEIN 10 KDA (IP-10), IS STIMULATED BY IFN-TAU AND RECRUITS IMMUNE CELLS IN THE OVINE ENDOMETRIUM. BIOLOGY OF REPRODUCTION. 2003. v. 68(4). p. 1413-1421. Interpretive Summary: Biochemical communications between the developing conceptus and the mammalian uterus are important for successful implantation. Interferon-tau (IFN-t), a protein produced by the conceptus prior to implantation in sheep and other ruminants, is considered to possess immune regulatory effects that permit a foreign protein (conceptus/embryo) to be implanted successfully in the uterus. The objective of this study was to examine a newly discovered uterine endometrial protein (IP-10) expressed during implantation. IP-10 mRNA expression was stimulated by IFN-t in a dose-dependent manner. Immunohistochemical analysis revealed that IP-10 protein was localized in luminal, glandular and sub-epithelial stroma cells of the pregnant sheep uterus and minimally detected in non-pregnant, cyclic sheep uterine tissue. These findings support the postulate that interaction of IFN-t and IP-10 is important in the establishment of immunological communication between the conceptus and maternal uterine tissue at the tim of implantation. Improved implantation can increase embryo survival and improve lambing rates for the sheep industry.
Technical Abstract: Biochemical communications between the conceptus and the mother are important for successful implantation and subsequent placentation. Interferon-tau (IFN-tau), an antiluteolytic protein produced by the trophoblast prior to implantation in ruminants, is considered to possess immunomodulatory effects. In cDNA subtraction analysis between uterine endometrium tissues from day 17 pregnant and day 15 cyclic ewes, ovine interferon-gamma-inducible protein 10 kDa (IP-10) that belongs to the C-X-C chemokine, family and lacks the glutamate-leucine-arginine (ELR) motif was identified. Results of Northern blot analysis revealed that the amounts of IP-10 mRNA were observed in the early pregnant endometrium and were much higher than in the cyclic uterine endometrium. Immunohistochemical analysis revealed that both IP-10 and IFN-gamma proteins were localized in the luminal epithelium, glandular epithelium and sub-epithelial stroma of pregnant uterus. Although both IP-10 and IFN-gamma proteins were localized in cyclic ewes, the intensities of IP-10 staining were minimal in the cyclic uterine endometrium. The expression of IP-10 mRNA by the monocytes was stimulated by IFN-alpha, IFN-gamma and IFN-tau in a dose-dependent manner, but IFN-tau was most effective in the enhancement of IP-10 mRNA. In the endometrial explants, the expression of IP-10 mRNA was also stimulated by IFN-tau at low levels. Taken together, these results suggest that the expression of ovine IP-10 observed in the early pregnant uterus could be induced by IFN-tau. These findings support the postulate that the interaction of IFN-tau and IP-10 is important in the establishment of immunological communication between the conceptus and maternal tissues.