CLONING OF LEUKEMIA INHIBITORY FACTOR (LIF) AND ITS EXPRESSION IN THEUTERUS DURING EMBRYONIC DIAPAUSE AND IMPLANTATION IN THE MINK (MUSTELA-VISON)

Leukemia inhibitory factor (LIF) is essential for embryo implantation in mice. Whether LIF plays a role in termination of embryonic diapause and initiation of implantation in carnivores, especially in species w ith obligate delayed implantation such as the mink, is not known. The objectives of this study were to clone the LIF coding sequence in the mink and determine its mRNA abundance in the uterus through embryonic diapause, implantation, and early postimplantation. We show that the m ink LIF cDNA contains 609 nt encoding a deduced protein of 203 amino a cids. The homologies are 80.6, 90, 88.2, 87.6, and 86.8% in coding seq uence and 79.2, 90.1, 91, 90.1 and 85.4% in amino acid sequence with m ouse, human, pig, cow, and sheep respectively. Glycosylation sites and disulfide bonds present in other species are generally conserved in t he mink LIF sequence. Quantitation by polymerase chain reaction amplif ication indicates that LIF mRNA is expressed in mink uterus just prior to implantation and during the first two days after implantation, but not during diapause or later after implantation pregnancy. The abunda nce of LIF mRNA was significantly higher in the uterus at the embryo e xpansion stage (P < 0.05) than at days 1-2 of postimplantation. By imm unohistochemical localization it was shown that LIF is expressed in th e uterine epithelial glands at time of embryonic expansion and in earl y postimplantation. The coincidence of LIF expression with implantatio n in this species suggests that LIF is involved in the implantation pr ocess, and may be a maternal signal which terminates obligate embryoni c diapause. Mel. Reprod. Dev. 51:13-21, 1998. (C) 1998 Wiley-Liss, Inc .