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a Reproductive Molecular Research Group, Department of Obstetrics and Gynaecology, University of Cambridge, Rosie Maternity Hospital, Cambridge CB2 2SW, United Kingdom
b Research Group in Human Reproductive Immunobiology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom
Mice in which the gene that encodes the receptor (R) for leukemia inhibitory factor (LIF) has been deleted show abnormal growth and development of the placenta. This indicates that LIF plays an important role in placental development. The expression of LIF-R and LIF was examined in human trophoblast and decidua using in situ hybridization and immunocytochemistry. LIF-R mRNA and immunoreactivity was localized in villous and extravillous trophoblast 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 invades the maternal decidua, therefore expresses LIF-R as it moves past decidual leukocytes, which express LIF mRNA. The effect of LIF on cultured human trophoblast was examined in vitro. Recombinant human LIF had no effect on [3H]thymidine incorporation by purified extravillous trophoblast, nor on expression of integrins 
1, 5, or ß1 by isolated trophoblast. These results identify fetal endothelial cells and all cells of the trophoblast lineage as targets for the action of LIF in human placenta. Although its effects on trophoblast are not yet clear, LIF appears to mediate interactions between maternal decidual leukocytes and invading trophoblast. LIF may also play a critical role in controlling angiogenesis in the placental villi, since human fetal endothelial cells express LIF-R, and mice lacking a functional LIF receptor gene show altered vascular development in the placenta.
2 Correspondence: Andrew Sharkey, Department of Obstetrics and Gynaecology, University of Cambridge, Box 223, Rosie Maternity Hospital, Robinson Way, Cambridge CB2 2SW, UK. FAX: 44 1223 215327; ams{at}mole.bio.cam.ac.uk
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