Localization of leukemia inhibitory factor and its receptor in human placenta throughout pregnancy

Mice in which the gene that encodes the receptor (R) for leukemia inhibitor y factor (LIF) has been deleted show abnormal growth and development of the placenta. This indicates that LIF plays an important role in placental dev elopment. The expression of LIF-R and LIF was examined in human trophoblast and decidua using in situ hybridization and immunocytochemistry. LIF-R mRN A and immunoreactivity was localized in villous and extravillous trophoblas t throughout pregnancy, and in endothelial cells of the fetal villi. Strong expression of mRNA encoding LIF was detected in decidual leukocytes, which are abundant at the implantation site. Extravillous trophoblast, which inv ades the maternal decidua, therefore expresses LIF-R as it moves past decid ual leukocytes, which express LIF mRNA. The effect of LIF on cultured human trophoblast was examined in vitro. Recombinant human LIF had no effect on [H-3]thymidine incorporation by purified extravillous trophoblast, nor on e xpression of integrins alpha 1, alpha 5, or beta 1 by isolated trophoblast. These results identify fetal endothelial cells and all cells of the tropho blast lineage as targets for the action of LIF in human placenta. Although its effects on trophoblast are not yet clear, LIF appears to mediate intera ctions between maternal decidual leukocytes and invading trophoblast. LIF m ay also play a critical role in controlling angiogenesis in the placental v illi, since human fetal endothelial cells express LIF-R, and mice lacking a functional LIF receptor gene show altered vascular development in the plac enta.