Immune Tolerance of the Human Decidua

Abstract

The endometrium is necessary for implantation, complete development of the placenta, and a successful pregnancy. The endometrium undergoes repeated cycles of proliferation, decidualization (differentiation), and shedding during each menstrual cycle. The endometrium—including stromal, epithelial, vascular endothelial, and immune cells—is both functionally and morphologically altered in response to progesterone, causing changes in the number and types of immune cells. Immune cells make up half of the total number of endometrial cells during implantation and menstruation. Surprisingly, immune tolerant cells in the endometrium (uterine natural killer cells, T cells, and macrophages) have two conflicting functions: to protect the body by eliminating pathogenic microorganisms and other pathogens and to foster immunological change to tolerate the embryo during pregnancy. One of the key molecules involved in this control is the cytokine interleukin-15 (IL-15), which is secreted by endometrial stromal cells. Recently, it has been reported that IL-15 is directly regulated by the transcription factor heart- and neural crest derivatives-expressed protein 2 in endometrial stromal cells. In this review, we outline the significance of the endometrium and immune cell population during menstruation and early pregnancy and describe the factors involved in immune tolerance and their involvement in the establishment and maintenance of pregnancy.

Increased uterine androgen receptor protein abundance results in implantation and mitochondrial defects in pregnant rats with hyperandrogenism and insulin resistance

“…Our data suggest that the inhibition of DHT + INS-induced uterine inflammation is at least partly dependent on decreased AR protein and blocked AR signaling. It has long been recognized that decidual immune cells such as uterine natural killer (uNK) cells and macrophages contribute to appropriate embryo implantation and successful pregnancy, and alterations in these cell populations may be associated with pregnancy-related complications [ 71 ]. Substantial evidence indicates that PCOS patients have aberrant/altered circulating levels of immune cells and uNK cell abundance in the uterus during the secretory phase of the menstrual cycle [ 8 , 72 ].…”

Decreased Expression of Cytotoxic Proteins in Decidual CD8+ T Cells in Preeclampsia

“…Decidua is a place of great immune importance. It is the site of direct contact of trophoblasts with maternal immunocompetent cells [10][11][12]. Immune cells that inhabit the decidua not only maintain placental function, but control trophoblast invasion, prevent fetal rejection, and participate in defense against infections during pregnancy [13,14].…”

Increased Uterine Androgen Receptor Protein Abundance Results in Implantation and Mitochondrial Defects in Pregnant Rats with Hyperandrogenism and Insulin Resistance

“…Our data suggest that the inhibition of DHT + INS-induced uterine in ammation is at least partly dependent on decreased AR protein and blocked AR signaling. It has long been recognized that decidual immune cells such as uterine natural killer (uNK) cells and macrophages contribute to appropriate embryo implantation and successful pregnancy, and alterations in these cell populations may be associated with pregnancy-related complications [65]. Substantial evidence indicates that PCOS patients have aberrant/altered circulating levels of immune cells and uNK cell abundance in the uterus during the secretory phase of the menstrual cycle [8,66].…”