The Role of Maternal Macrophages in the Developing Decidua and Placenta
2Veterinary Resources, Weizmann Institute of Science
3Life Sciences Core Facilities, Weizmann Institute of Science
About a fifth of human pregnancies end in miscarriage. Recurrent spontaneous abortions are closely linked to immune impairments during implantation, decidualization, and placentation. Maternal immune cells constitute half of the cells within the uterus during decidualization, of which a quarter are macrophages, shown to have pivotal roles in the processes of implantation and vascular remodeling during placental development. Tissue macrophages in the developing decidua can arise from maternal resident macrophages in the myometrium or from circulating maternal monocytes that enter the decidua during implantation. Our study focuses on unraveling the origin of specific decidual macrophage subpopulations and their functional contribution to placental development.
We aim to unravel the origin and functions of various sub-types of macrophages and their contribution to placental development. To study the role of monocyte-derived macrophages during early gestational stages, we set to deplete monocytes by using an anti-chemokine-receptor 2 antibody. Pregnancies were verified by ultrasound on day E6.5, and mice were sacrificed on E7.5. Implantation sites were cryo-sectioned for Immunohistochemistry analysis using antibodies to macrophages (CD206, Iba1 or F4/80), and endothelial cells (CD31 for mature and CD34 for immature). Similarly, placentas at E14.5 were isolated to follow the consequence of monocyte depletion at early gestational age. In addition, to better define the various types of macrophages in the developing placenta and their spatial localization, we used mouse models such as Cx3cr1GFP, Lyve1ncre/ Slc40a1ncre ;Cx3cr1ccre;R26-tdTomato that enable fate mapping, origin and spatial localization of the cells within the developing placenta.
Based on our preliminary results we observed distinct populations of macrophages in the decidua. Upon monocytes depletion we did not observe a change in the pattern of macrophages located in the myometrium, however, in the decidua some embryos showed reduction of macrophages. In addition, we saw changes in the pattern of CD31 and CD34 staining in the developing decidua. This may suggest that maternal monocyte derived macrophages have a role in maternal vasculature development during early gestation. Furthermore, at E14.5 monocyte depletion at early gestational age led to higher number of absorbed embryos indicating the importance of maternal monocyte derived macrophages for proper placental and embryonic development.