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

Abstract

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.

Keywords: Early gestation; embryo implantation; endometrium; interleukin-1.