Primitive RBCs enucleate in the placental stroma in close association with placental macrophages. (A) Immunohistochemical staining of 6.5-week placental sections for macrophages (FXIII, blue), RBCs (CD235, brown), endothelial cells (CD34, red), and trophoblast (cytokeratin, purple) demonstrated the congregation of macrophages and RBCs in the extravascular stroma in placental villi (i; a higher magnification inset of the boxed area is also shown), whereas at the same developmental age very few macrophages were found in the fetal liver (ii). Images were acquired at 200× original magnification. (B) EM performed on 7-week placental villi demonstrated both direct physical interactions between placental macrophages and erythroblasts (i). Dashed arrows indicate macrophage cytoplasmic projection, solid arrow denotes ejected nucleus; M, macrophage; E, erythroid cell. as well as macrophages containing ingested nuclei (i′ inset) and pyrenocytes in circulation (ii inset). These macrophage-RBC associations were reminiscent of RBC maturation during definitive erythropoiesis in the fetal liver, where both free pyrenocytes (iii arrow) and engulfed nuclei (iii′ arrow; Eb, erythroblast) were present. All original magnifications for EM micrographs are as indicated.