The integrative roles of chemokines at the maternal–fetal interface in early pregnancy

Abstract

Embryos express paternal antigens that are foreign to the mother, but the mother provides a special immune milieu at the fetal-maternal interface to permit rather than reject the embryo growth in the uterus until parturition by establishing precise crosstalk between the mother and the fetus. There are unanswered questions in the maintenance of pregnancy, including the poorly understood phenomenon of maternal tolerance to the allogeneic conceptus, and the remarkable biological roles of placental trophoblasts that invade the uterine wall. Chemokines are multifunctional molecules initially described as having a role in leukocyte trafficking and later found to participate in developmental processes such as differentiation and directed migration. It is increasingly evident that the gestational uterine microenvironment is characterized, at least in part, by the differential expression and secretion of chemokines that induce selective trafficking of leukocyte subsets to the maternal-fetal interface and regulate multiple events that are closely associated with normal pregnancy. Here, we review the expression and function of chemokines and their receptors at the maternal-fetal interface, with a special focus on chemokine as a key component in trophoblast invasiveness and placental angiogenesis, recruitment and instruction of immune cells so as to form a fetus-supporting milieu during pregnancy. The chemokine network is also involved in pregnancy complications.

TNF-α alters the inflammatory secretion profile of human first trimester placenta

“…Although largely considered as inflammatory factors, it is worth noting that IL-8 and CCL2 have recently been suggested to regulate a number of non-inflammatory functions in human early pregnancy. 49 Both, IL-8 and CCL2 derived from human villous first trimester trophoblasts were shown to enhance multistep processes of angiogenesis such as permeability, migration, proliferation, and capillary tube formation of human endometrial microvascular endothelial cells. 50 Although abundant IL-6 and IL-8 secretion under basal conditions is in good agreement with other studies, results from our explant experiments suggest that secretion of both IL-6 and IL-8 is not considerably affected by exogenous TNF-α in human first trimester placenta.…”

Continuous model of conceptus implantation to the maternal endometrium

“…In mice, expression of wingless-type MMTV integration site family (WNTs) is found in the uterus and its expression at luminal epithelium depends on the presence of blastocysts (Mohamed et al 2005). It is increasingly evident that chemokines are involved in intracellular communication and signal transduction at the maternal-fetal interface (Du et al 2014). For example, chemokine ligand CXCL12, expressed by cytotrophoblasts, binds to CXCR4, CXCR7 and syndecan-4 receptors, mediating cell migration, directed invasion, proliferation and survival (Schanz et al 2011).…”

Immune regulation at the fetal‐maternal interface with focus on decidual macrophages

“…Although chemokines have gained much interest in several aspects of reproductive immunology (Du et al, 2014b), the role of decidual macrophages in contributing to the chemokine environment and the positioning of cells within the decidua has been surprisingly overlooked. NK cells have been attributed the ability to direct trophoblast invasion through production of the chemokines CXCL10 and CXCL8 and the interaction with their receptors CXCR3 and CXCR1 on trophoblast cells (Hanna et al, 2006).…”