Leukemia inhibitory factor (LIF) is a secreted 38- to 67-kDa glycoprotein first named for its ability to inhibit proliferation of the murine myeloid leukemic cell line M1. Messenger RNA for LIF has been detected in a variety of adult mouse tissues, but is most abundant in the uterus. LIF mRNA and immunoreactive protein increase significantly in the endometrial glands at the time of implantation in the mouse but rapidly decline during the postimplantation period. Uterine LIF expression during pseudopregnancy in the mouse is identical to that of pregnancy, indicating that its expression is maternally regulated. The expected rise in LIF mRNA on Day 4 does not occur during delayed implantation in the mouse despite the presence of viable embryos. buy cheap antibiotics
Upon termination of delay, LlF mRNA is again expressed. These data reveal an intimate relationship between uterine LIF and embryo implantation that appears to be controlled by maternal hormones. Evidence that LIF expression is critical for successful pregnancy has been provided by the LIF knockout mouse. Normal and LIF-deficient blastocysts hatch from the zona pellucida but fail to implant in LIF females. Transfer of the embryos to pseudopregnant wild-type females results in successful implantation and development to term. Continuous infusion of recombinant LIF results in uterine decidualization and implantation in LIF females. However, blastocysts that are homozygous for the inactivated LIF receptor (3 (LIFRp) gene successfully implant. These data indicate that maternal LIF is not required for blastocyst development but may be needed to prepare the uterus for implantation.