Physiologic Events of Embryo Implantation and Decidualization in Human and Non-Human Primates

Abstract

Reproduction is a fundamental process for the preservation of the human species. This process requires a sequence of orchestrated events that are necessary for a successful pregnancy. Two of the most critical steps in the establishment of human pregnancy are implantation and decidualization, which are required for maternal interactions with the developing embryo. This review primarily highlights the physiological aspects of these two events and the adverse pregnancy outcomes from defective implantation and decidualization. The focus of this review is to provide a general concept of the mechanisms involved during the window of implantation, description of components involved in the process and possible pathologies that could disrupt the embryo implantation and decidualization and specifically as it applies to women and non-human primates.

Keywords: Notch; cytokines; decidualization; embryo; endometrium; gynecological pathologies; implantation; miRNA; primates.

Figure 1

Human implantation is a process that could be divided into apposition, adhesion/attachment and invasion/penetration. During apposition (A), the blastocyst expresses L-selectins. The presence of Mucin-1 (MUC-1) repels the blastocyst and prevents it from attaching outside of the window of uterine receptivity. The L-selectins interact with the L-selectin ligands, which are expressed mainly on the pinopodes during the implantation window. At the beginning of the adhesion phase (B), the blastocyst promotes the cleavage of MUC-1 at the implantation site to ensure successful attachment. Cytokines such as Leukemia inhibitory factor (LIF), play an important role during human implantation by supporting the embryo-endometrial interactions. During the invasion or penetration phase (C), the trophoblast cells from the blastocyst penetrate the endometrial epithelium into the stroma. The extra-villous trophoblast cells start proliferating and differentiate into inner cytotrophoblast and outer syncytiotrophoblast. Once implantation is initiated and the embryo breaches the luminal epithelium, the stromal cells surrounding the embryo transform into decidualized cells (D). Immune cells such as macrophages and uterine natural killer (uNK) cells play an important role during decidualization to promote an environment that is conducive to successful implantation. Some art elements used in this figure were obtained from Servier Medical art (http://smart.servier.com). Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License.