The Placenta in Toxicology. Part II

Abstract

During pregnancy, the maternal immune system is challenged by the semiallogeneic fetus, which must be tolerated without compromising fetal or maternal health. This review updates the systemic and local immune changes taking place during human pregnancy, including some examples in rodents. Systemic changes are induced by contact of maternal blood with placental factors and include enhanced innate immunity with increased activation of granulocytes and nonclassical monocytes. Although a bias toward T helper (Th2) and regulatory T cell (Treg) immunity has been associated with healthy pregnancy, the relationship between different circulating Th cell subsets is not straightforward. Instead, these adaptations appear most evidently at the fetal-maternal interface, where for instance Tregs are enriched and promote fetal tolerance. Also innate immune cells, that is, natural killer cells and macrophages, are enriched, constituting the majority of decidual leukocytes. These cells not only contribute to immune regulation but also aid in establishing the placenta by promoting trophoblast recruitment and angiogenesis. Thus, proper interaction between leukocytes and placental trophoblasts is necessary for normal placentation and immune adaptation. Consequently, spontaneous maladaptation or interference of the immune system with toxic substances may be important contributing factors for the development of pregnancy complications such as preeclampsia, preterm labor, and recurrent miscarriages.

Trophoblast Induces Monocyte Differentiation Into CD14+/CD16+ Macrophages

“…We show that after education, phagocytosis as well as endometrial stromal repair, two established functions of M2 macrophages, was significantly enhanced in TEMs as compared to peripheral monocytes and MCSF-derived macrophages (data not shown). Tissue integrity and abnormal clearance of apoptotic debris have contributed to complications such as preeclampsia and IUGR 8, 47 , which are both associated with trophoblast dysfunction. This further drives the importance of trophoblast cross talk as contributing to the normal function of local macrophages.…”

“…The maternal-fetal interface is made of both placental and decidual tissue and within this tissue are components of the maternal immune system 8, 9 . One the most abundant immune cells present throughout pregnancy are macrophages, accounting for 20–25% of the total leukocyte population in the first trimester 10, 11 and maintaining their presence throughout pregnancy.…”

M1/M2 Macrophage Polarity in Normal and Complicated Pregnancy

“…Prior to embryo implantation, the endometrium begins to undergo structural changes referred to as decidualization, which is initiated by increased progesterone levels (44, 45). The process of decidualization in human beings stabilizes by 12 weeks gestation (46). The physical changes that occur during decidualization include proliferation of luminal epithelium, development of secretory glandules with large apical protrusions (pinopodes) and microvilli, and transformation of fibroblast-like endometrial stromal cells into larger rounded cells (47, 48).…”

Monocytes and Macrophages in Pregnancy and Pre-Eclampsia

“…These macrophages and NK cells may have a local immune function, however, they also appear to be important for placental development by promoting trophoblast recruitment, spiral artery remodeling, and angiogenesis (11). The present review will focus on macrophages at the maternal–fetal interface.…”

“…The present review will focus on macrophages at the maternal–fetal interface. In normal pregnancy, most of the macrophages at the maternal–fetal interface are M2 macrophages, i.e., immunomodulatory macrophages (11). In pre-eclampsia, there appear to be increased numbers of M1 macrophages, suggesting a role for these macrophages in the poor placental development in pre-eclampsia.…”