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 embryonic growth and a common site of ectopic implantation. Although the factors responsible for early embryogenesis and implantation are incompletely understood, leukemia inhibitory factor may have an important role in early embryonic development and implantation. We set out to evaluate the production and modulation of leukemia inhibitory factor in the fallopian tube.


METHODS
We first investigated leukemia inhibitory factor messenger ribonucleic acid levels in fallopian tubes. We then investigated leukemia inhibitory factor messenger ribonucleic acid and protein production in tubal epithelial and stromal cell cultures.


RESULTS
Leukemia inhibitory factor messenger ribonucleic acid is expressed in the fallopian tube with only slight variation during the menstrual cycle; however, it is markedly elevated in association with ectopic pregnancy. The level is higher in the tubal mucosa than in the remaining layers and is higher in the more distal segments of the fallopian tube. Estradiol and progesterone did not modulate leukemia inhibitory factor expression in epithelial or stromal cell cultures. Interleukin-1 alpha, tumor necrosis factor-alpha, and transforming growth factor-beta enhanced leukemia inhibitory factor expression in epithelial and stromal cells, with transforming growth factor-beta 1 enhancing expression 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 with transforming growth factor-beta alone or in combination with epidermal growth factor and platelet-derived growth factor, as well as TNF-alpha alone or in combination with interleukin-1 alpha enhanced secretion of leukemia inhibitory factor at or above the levels found with epithelial cells.


CONCLUSIONS
We speculate that the high constitutive levels 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 marked induction of secretion in the tubal stroma by growth factors and cytokines suggest a link between inflammation, leukemia inhibitory factor, and tubal ectopic pregnancies.
Keltz
M D
MD
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT 06520-8063, USA.
Attar
E
E
Buradagunta
S
S
Olive
D L
DL
Kliman
H J
HJ
Arici
A
A
D000328:Adult; D001790:Blood Physiological Phenomena; D002478:Cells, Cultured; D003470:Culture Media; D016207:Cytokines / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism; D005187:Fallopian Tubes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D006131:Growth Inhibitors / Q000235:genetics* / Q000378:metabolism*; D006133:Growth Substances / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D011247:Pregnancy; D011271:Pregnancy, Ectopic / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism
D003470:Culture Media; D016207:Cytokines; D006131:Growth Inhibitors; D006133:Growth Substances; D006728:Hormones; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D012333:RNA, Messenger