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.