Interleukin-11 expression: its significance in eutopic and ectopic human implantation.
Embryo implantation and subsequent decidualization, trophoblast invasion and formation of a functional placenta are crucial for establishment and maintenance of pregnancy. Interleukin-11 signalling has been shown to be obligatory for adequate decidualization and trophoblast invasion in mice. Defects in IL-11 signalling in mice result in trophoblast over-invasion and fetal loss. The pathological situation of human tubal pregnancy resembles that of IL-11Ralpha(-/-) mice concerning these symptoms. As our interest is focused on the human early pregnancy, we compared IL-11 expression at the implantation site of ectopic tubal pregnancy (EP) to 1st and 2nd trimester of normal intrauterine pregnancies (IP), and to the normal cycling endometrium. The mRNA expression of IL-11 and IL-11Ralpha was analysed by semiquantitative RT-PCR. Protein expression was detected by western blotting and immunohistochemistry. IL-11Ralpha is expressed constitutively in all tissue specimens analysed. IL-11 is expressed predominantly during follicular and early luteal phase of the menstrual cycle. In IP, IL-11 expression peaks during the 1st trimester and declines from the beginning of the 2nd trimester onwards. In tubal abortions, IL-11 expression is reduced in comparison to vital EP and IP. Cultured primary endometrial and decidual epithelial cells were analysed for hormonal regulation of IL-11 by enzyme-linked immunosorbent assay and RT-PCR. IL-11 is up-regulated by estrogen and down-regulated by progesterone. Overall, our results indicate that in humans, IL-11 signalling is significantly involved in regulation of trophoblast invasion. In the case of tubal abortion, inadequate IL-11 signalling may therefore result in dysregulation of trophoblast invasion.
Department of Anatomy and Reproductive Biology, RWTH University of Aachen, Wendlingweg 2, 52057 Aachen, Germany. uvonrango@ukaachen.de
U
U
von Rango
J
J
Alfer
S
S
Kertschanska
B
B
Kemp
G
G
Müller-Newen
P C
PC
Heinrich
H M
HM
Beier
I
I
Classen-Linke
D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation; D010064:Embryo Implantation / Q000235:genetics / Q000502:physiology*; D004717:Endometrium / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D017370:Interleukin-11 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D053703:Interleukin-11 Receptor alpha Subunit; D008597:Menstrual Cycle / Q000235:genetics / Q000502:physiology; D051379:Mice; D011247:Pregnancy; D011264:Pregnancy Trimesters / Q000235:genetics / Q000378:metabolism; D011274:Pregnancy, Tubal / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D053702:Receptors, Interleukin-11; D015398:Signal Transduction; D015854:Up-Regulation
C508428:IL11RA protein, human; C508429:Il11ra1 protein, mouse; D017370:Interleukin-11; D053703:Interleukin-11 Receptor alpha Subunit; D018123:Receptors, Interleukin; D053702:Receptors, Interleukin-11