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Interleukin-1 receptor antagonist prevents embryonic implantation by a direct effect on the endometrial epithelium
C Simón1, D Valbuena, J Krüssel
1Instituto Valenciano de Infertilidad and Department of Pediatrics, Obstetrics, and Gynecology, Valencia University, Spain. ivi@futurnet.es
Objective:
To investigate the embryonic and/or endometrial molecular mechanisms underlying the antiimplantation effect of interleukin-1 receptor antagonist (IL-1ra).
Design:
Controlled experiment.
Setting:
Animal facilities at Stanford University and laboratories of the Instituto Valenciano de Infertilidad and the University of Sydney.
Animal(S):
Twelve-week-old B6C3F-1 female mice.
Intervention(S):
Intraperitoneal injections of recombinant human IL-1ra during the periimplantation period.
Main Outcome Measure(S):
Implantation sites, embryonic morphology, and viability. Polymerase chain reaction and immunohistochemistry for integrins and extracellular matrices and transmission electron microscopy of endometrium in IL-1ra-treated versus control animals.
Result(S):
Pregnancy rates in control and IL-1ra-injected animals were 60% and 13%, respectively. At day 8 of pregnancy, flushing of uteri obtained from the treated group resulted in 32 blastocysts. Six pseudopregnant animals received IL-1ra-treated blastocysts (left horn) and control blastocysts (right horn), resulting in one pregnancy, with two embryos and one embryo in the left and right horns, respectively. At day 4 of pregnancy, IL- 1ra down-regulated alpha4 mRNA with use of the polymerase chain reaction. Immunohistochemistry showed a decrease of alpha4, alpha v, and beta3, and transmission electron microscopy revealed inhibition of transformation of the plasma membrane.
Conclusion(S):
Impairment of embryonic adhesion with IL-1ra is mediated through a direct effect on transformation of the epithelial plasma membrane at the time of implantation as a result of down-regulation of alpha4, alpha v, and beta3.