The role of leukaemia inhibitory factor and interleukin-6 in human reproduction

Abstract

There is now strong evidence that many of the actions of steroids in controlling reproduction are mediated by locally acting factors such as growth factors and cytokines. These have been shown to act both in an autocrine and paracrine manner to regulate preimplantation embryo development and endometrial receptivity. They also regulate trophoblast differentiation and migration which is necessary for placental development. The creation of mouse strains lacking genes for receptors or growth factors has proved important in defining which of these are essential in reproduction in this species and those that play a lesser role. Using this approach, a lack of leukaemia inhibitory factor (LIF) in the murine endometrium has been shown to result in failed implantation. Evidence from infertile women supports the notion that abnormal expression of LIF, or the related cytokine interleukin-6 (IL-6) in the endometrium may underlie some forms of human infertility. This offers the opportunity for therapeutic intervention, if levels of these cytokines can be altered in a specific and controlled way. The recently described method of delivery of genes to the uterine epithelium provides a powerful new approach by which this could be achieved. The ability to regulate the function of specific genes in the endometrium by direct gene transfer raises the prospect of novel opportunities for therapeutic intervention.