MODULATION OF LEUKEMIA INHIBITORY FACTOR GENE-EXPRESSION AND PROTEIN-BIOSYNTHESIS IN THE HUMAN FALLOPIAN-TUBE

OBJECTIVE: The fallopian tube is the site of fertilization and early e mbryonic growth and a common site of ectopic implantation. Although th e factors responsible for early embryogenesis and implantation are inc ompletely understood, leukemia inhibitory factor may have an important role in early embryonic development and implantation. We set out to e valuate the production and modulation of leukemia inhibitory factor in the fallopian tube. STUDY DESIGN: We first investigated leukemia inhi bitory factor messenger ribonucleic acid levels in fallopian tubes. We then investigated leukemia inhibitory factor messenger ribonucleic ac id and protein production in tubal epithelial and stromal cell culture s. RESULTS: Leukemia inhibitory factor messenger ribonucleic acid is e xpressed in the fallopian tube with only slight variation during the m enstrual cycle; however, it is markedly elevated in association with e ctopic pregnancy. The level is higher in the tubal mucosa than in the remaining layers and is higher in the more distal segments of the fall opian tube. Estradiol and progesterone did not modulate leukemia inhib itory factor expression in epithelial or stromal cell cultures. Interl eukin-1 alpha, tumor necrosis factor-alpha, and transforming growth fa ctor-beta enhanced leukemia inhibitory factor expression in epithelial and stromal cells, with transforming growth factor-beta 1 enhancing e xpression by fourfold in stromal cells. Epithelial cells secreted high levels of leukemia inhibitory factor compared with stromal cells (332 +/- 89 vs 25 +/- 42 pg/mg total protein). Yet stromal cells treated w ith transforming growth factor-beta alone or in combination with epide rmal growth factor and platelet-derived growth factor, as well as TNF- alpha alone or in combination with interleukin-1 alpha enhanced secret ion of leukemia inhibitory factor at or above the levels found with ep ithelial cells. CONCLUSIONS: We speculate that the high constitutive l evels of leukemia inhibitory factor expressed in the ampullary portion of the fallopian tube may play a role in early embryonic development. Additionally, elevated expression with ectopic implantation and the m arked induction of secretion in the tubal stroma by growth factors and cytokines suggest a link between inflammation, leukemia inhibitory fa ctor, and tubal ectopic pregnancies.