Synchronous regulation of the determinants of endometrial receptivity to interleukin 1 at key stages of early embryo implantation in vivo

Objective: To investigate the expression kinetics of interleukin- 1 receptors (IL- 1R), receptor antagonist (IL- 1RN), and monocyte chemotactic protein 1 (MCP-1) throughout early gestation in mice. Design: Assessment of IL- 1R, IL- 1RN, and MCP- 1 throughout early pregnancy. Setting: Reproduction laboratory. Animal(s): B6C3F1 female mice bred with fertile males of the same strain. Intervention(s): Collection of endometrial tissue at necropsy from nonimplanted and implanted sites. Main Outcome Measure(s): IL- 1R, IL- 1RN, and MCP- 1 mRNA expression by quantitative reverse-transcription polymerase chain reaction and protein expression by enzyme-linked immunosorbent assay and immunohistochemistry. Result(s): The expression of the signaling IL- 1R1 significantly increased in the first 2 days of gestation, which corresponded to the inflammatory-like period triggered by the seminal fluid, before increasing again at the implantation window and lasting throughout embryo implantation. The expression of inhibitory IL- 1R2 and IL- 1RN concomitantly increased during gestational days 1-2 but remained low, particularly within the embryo implantation sites and throughout the implantation period. The expression of MCP- 1 significantly increased only at the embryo implantation sites and showed a significant positive correlation with IL- 1R1 expression. Conclusion(s): Our data identified for the first time synchronous changes in endometrial IL- 1R throughout early gestation in vivo and point to a deep modulation of endometrial receptivity to IL- 1 by embryo-driven signals. This may play a key role in the creation of a receptive phenotype in the maternal endometrium and represent a key mechanism underlying embryo implantation. (C) 2014 by American Society for Reproductive Medicine.