LIF-STAT signaling and trophoblast biology

Abstract

Leukemia inhibitory factor (LIF) is a pleiotropic growth factor that regulates several biological functions. This review focuses on the LIF-dependent STAT activation and its impact on modulation of trophoblast functions during embryo implantation. LIF is mainly produced by the maternal endometrium at the time of implantation while its receptors are present both on the endometrium and trophoblasts. It might influence blastocyst attachment through STAT3 activation and expression of integrins. After attachment of the blastocyst, trophoblasts undergo proliferation and differentiation into invasive EVTs and non-invasive STBs. Under in vitro conditions, LIF regulates all these processes through activation of STAT- and MAPK-dependent signaling pathways. The observations that LIF and STAT3 knockout mice are infertile further strengthen the notion about the critical involvement of LIF-mediated signaling during embryo implantation. Hence, a better understanding of LIF-STAT signaling would help in improving fertility as use of LIF in in vitro blastocyst culture improves the implanting ability of blastocyst after IVF.

Lineage specification and pluripotency revealed by transcriptome analysis from oocyte to blastocyst in pig

“…36 In our analysis, the expression of LIFR was low in the ICM. The pathway can be activated by the members of IL6 family, such as LIF and IL6.…”

Autocrine Loop Involving IL-6 Family Member LIF, LIF Receptor, and STAT4 Drives Sustained Fibroblast Production of Inflammatory Mediators

“…In a murine model of arthritis, Lif deficient mice were shown to have a reduction in clinical arthritis severity compared to wild-type disease controls (Upadhyay et al, 2012). Although LIF has been reported to be produced by fibroblasts (Suman et al, 2013), its autocrine role on IL-6 regulation following inflammatory stimulation was not previously known. In addition, other autocrine signaling involving IL-6 – IL-6R and STAT3 circuit has been described for fibroblasts (Ogura et al, 2008).…”

MicroRNAs in spent blastocyst culture medium are derived from trophectoderm cells and can be explored for human embryo reproductive competence assessment

“…Furthermore, new communication systems mediating the cross-talk between the blastocyst and the endometrium based on secreted miRNAs have been recently discovered in animal models. In particular, LIFdependent STAT activation and its impact on modulation of trophoblast functions during embryo implantation was described in several animal models (17)(18)(19)(20) and recently direct evidence of the role of miR-181 secreted by endometrial cells in modulating embryo implantation through the regulation of LIF has been reported in mice (21).…”