Despite of the claim that maternal leukemia inhibitory factor (LIF) - a member of interleukin 6 (IL6) family of cytokines - plays indispensable roles for murine embryo implantation, these roles remain undefined in humans because the potency of LIF on implantation appears to vary among individuals. Here, we showed that the contribution of LIF for murine implantation was dependent on the strains of mice (ICR, C57BL/6J (B6), ddY, BALB/c, DBA/2Cr and MF1 strains). Inhibition of LIF during the implantation period caused severe disruption of embryo implantation in B6 and MF1 strains. Implantation was partly disrupted in other strains, but some embryos were implanted successfully. We speculated that other IL6 family members compensate for LIF actions on implantation in ICR, ddY, BALB/c, and DBA/2Cr strains. Indeed, the expression level of Ctf1 was upregulated by blockage of LIP function. CT-1 (encoded by Ctf1) treatment induced successful implantation without LIF in delayed implantation mice (ICR and B6) via phosphorylation of the signal transducer and activator of transcription 3 (STAT3) in the uterine luminal epithelium. Simultaneous inhibition of LIP and CT-1 did not block implantation completely in ICR mice, indicating that embryo implantation in this strain was robustly protected by LIP, CT-1 and other potential STAT3 activators. The present study might provide an explanation for the individual variation in the potency of LIF for embryo implantation in humans. (c) 2014 Elsevier GmbH. All rights reserved.