The Role of Decidual Macrophages During Normal and Pathological Pregnancy

Abstract

Macrophages perform many specific functions including host defense, homeostasis, angiogenesis, and tissue development. Macrophages are the second most abundant leukocyte population in the non-pregnant endometrium and pregnant decidua and likely play a central role in the establishment and maintenance of normal pregnancy. Importantly, aberrantly activated uterine macrophages can affect trophoblast function and placental development, which may result in various adverse pregnancy outcomes ranging from pre-eclampsia to fetal growth restriction or demise. Only by fully understanding the roles of macrophage in pregnancy will we be able to develop interventions for the treatment of these various pregnancy complications. This review discusses the general origin and classification of monocytes and macrophages and focuses on the phenotype and functional roles of decidual macrophage at the maternal-fetal interface in normal pregnancy, as well as discussing the potential contribution of the abnormal state of these cells to various aspects of pregnancy pathologies.

Immunology of hepatic diseases during pregnancy

“…Dysfunctional or aberrantly activated decidual macrophages seem to be of central importance for PE development [90,91]. Activated macrophages were found in increasing numbers at spiral arteries of PE patients while the trophoblast invasion was shown to be decreased [92].…”

“…TNFα is able to induce apoptosis in trophoblast cells. An additional activation of the inducible nitric oxide synthesis may further support placental damage [90].…”

“…In addition, aberrant type-1 macrophage activation resulting from inadequate immune tolerance to fetal antigens may account for pregnancy associate complications [90]. Dysfunctional or aberrantly activated decidual macrophages seem to be of central importance for PE development [90,91].…”

Emerging role for dysregulated decidualization in the genesis of preeclampsia

“…Importantly, dNK cells likely play key roles in promoting trophoblast invasion and spiral artery remodeling [34–36]. As well, increased decidual and myometrial macrophage number of an alternatively-activated (“M2”) phenotype accumulate [37], and T regulatory cells are also believed to exert an important role in uterine immune tolerance to the fetal/placental semi-allograft [38]. Fundamentally, decidualization is preparation of the “soil” for the “seed” (embryo implantation and placentation).…”

“…Alternatively, the inner one-third of the myometrium may also undergo a kind of “decidualization”, which is compromised in women who develop preeclampsia, thereby precluding deep extravillous trophoblast invasion [29]. NK cells confined to the decidua may play a major role in orchestrating extravillous trophoblast invasion and spiral artery remodeling in the decidua ( vide supra ), while uterine macrophages also present in the inner one-third of the myometrium, could conceivably play a similar role in this region of the placental bed [37]. With impairment of decidualization, the optimal number and phenotype of these immune cells residing in the decidua and myometrium would be compromised.…”