The Multifaceted Actions of Leukaemia Inhibitory Factor in Mediating Uterine Receptivity and Embryo Implantation

Abstract

CitationRosario GX, Stewart CL. The multifaceted actions of leukaemia inhibitory factor in mediating uterine receptivity and embryo implantation. Am J Reprod Immunol 2016; 75: 246-255 doi:10.1111/aji.12474 Embryo implantation is mediated by the combined actions of the ovarian hormones E 2 and P4 on the uterus. In addition, the pro-inflammatory cytokine, leukaemia inhibitory factor (LIF), plays a pivotal role in regulating uterine receptivity. LIF is expressed in the endometrial glands and has a robust action on the uterine luminal epithelium (LE). In mice, LIF is induced by nidatory E 2 and functions to convert the LE from a non-receptive to an embryo-responsive state. LIF mediates its actions by activating the JAK-STAT pathway specifically in the LE. Activation of JAK-STAT pathway results in the induction of many additional pathways, including some 40 + transcription factors, many of which initiate a cascade of changes affecting epithelial polarity, epithelial-mesenchymal interactions, angiogenesis, stromal cell decidualization, and inhibiting cell proliferation. This review discusses the role of LIF and the recent analysis of its action on the uterine LE in regulating endometrial receptivity and implantation.

Leukemia Inhibitory Factor Represses GnRH Gene Expression via cFOS during Inflammation in Male Mice

“…However, its functions are not limited to inflammation: LIF has been demonstrated to play a crucial, non-redundant role in embryo implantation in both mice and humans [44-46]. LIF also maintains stem cells and regulates differentiation of germ cells [47, 48].…”

The ameliorating effects of Bushen Tiaoxue Granules and Kunling Wan on impaired angiogenesis and endometrial receptivity in rats following controlled ovarian hyperstimulation

“…19,42 LPA3 signaling is highly dependent on female sex hormones, P4 and E2. 19,42 LPA3 signaling is highly dependent on female sex hormones, P4 and E2.…”

“…Under the influence of ovarian hormones, several VEGF upstream molecules have been proved to participate in the process of early fetal-maternal interaction. [17][18][19] Studies have identified that vascular remodeling is fundamental at the maternal-fetal interface and LPA3 participates in the process of vascularization. 16 Previous results revealed that receptive state in the mouse uterus depends on LIF, which activates Janus kinase-signal transducer and activator of transcription 3 pathway and thus affects a cascade of events including angiogenesis therefore engaging in embryo implantation.…”

“…16 Previous results revealed that receptive state in the mouse uterus depends on LIF, which activates Janus kinase-signal transducer and activator of transcription 3 pathway and thus affects a cascade of events including angiogenesis therefore engaging in embryo implantation. [17][18][19] Studies have identified that vascular remodeling is fundamental at the maternal-fetal interface and LPA3 participates in the process of vascularization. 20,21 Controlled ovarian hyperstimulation might affect the expression of endometrial receptivity-related molecules in infertility patients and eventually diminish endometrial receptivity.…”

Involvement of serum glucocorticoid‐regulated kinase 1 in reproductive success

“…Decidualization is one of the most important post‐implantation events that support embryonic development and provide nutrients until a functional placenta is formed (50, 51). Primarily induced by P4, endometrial stromal cells differentiate into secretory decidual cells at the time of blastocyst attachment to the uterine epithelium (52).…”