The Microenvironment of Human Implantation: Determinant of Reproductive Success

Abstract

Successful implantation requires synchronous development of embryo and endometrium. Endometrial receptivity results from progesterone-induced differentiation of endometrial cells, generally achieved during the mid-secretory phase of the cycle. Failure to properly develop receptivity results in failed or inadequate implantation and hence no ongoing pregnancy. The blastocyst undergoes final development, apposition, attachment and initiates invasion of the endometrial epithelium within the uterine cavity. Thus, the microenvironment provided by uterine fluid, particularly glandular secretions, is essential for implantation. Analysis of endometrial fluid has identified cytokines, chemokines, proteases, antiproteases and other factors that modulate blastocyst functions relevant to implantation. Exosomes/microvesicular bodies released from the endometrium (and likely also the embryo) are present in uterine fluid. These can transfer miRNA, proteins and lipids between cells, thus providing endometrial-embryo communication in the peri-implantation period. Understanding the uterine microenvironment, and its effects on endometrial-embryo interactions, will provide opportunities to modify current infertility treatments to improve success rates.

Adolescence and the next generation

“…Extracellular vesicles produced by the endometrium have been shown to be mediators of maternal-embryo communication through their protein and RNA cargoes 80 . Secreted proteins from both the embryo (for example, human chorionic gonadotrophin from the trophectoderm) and endometrium (for example, cytokines) guide successful implantation 81 . These processes are sensitive to maternal hormonal status and environmental influences, including stress and nutrition 82 .…”

Direct Cell–Cell Interactions in the Endometrium and in Endometrial Pathophysiology

“…The luminal epithelium is transformed from a non-receptive to a receptive state, which allows adhesion and invasion of the trophoblast [3,28], while the glandular epithelium produces the components of the uterine fluid indispensable for the survival of the early embryo [29]. In parallel, the stromal cells differentiate to pre-decidual cells in preparation for trophoblast invasion [4].…”

Extracellular Vesicles in the Intrauterine Environment: Challenges and Potential Functions

“…Uterine fluid in all species contains a rich abundance of nutrients, along with regulatory proteins, lipids, and RNA moieties. While many of these are selectively derived from blood or from tubal fluid, a large number of the proteins are derived from the endometrium and their concentrations vary with the time of the menstrual cycle (summarized in [1]).…”