Murine CD200+CK7+ trophoblasts in a poly (I:C)-induced embryo resorption model

Abstract

Cytokeratin 7 (CK7) is currently regarded as the best marker for trophoblast cells, while CD200 (OX-2), known as ‘tolerance signal’, plays an important role in normal pregnancy. In this study, the status of CD200 expression was investigated in BALB/c × C57BL/6 and BALB/c × BALB/c mating combinations designed as allogeneic and syngeneic murine models of induced embryo resorption, in which the resorption rate was boosted by an i.p. injection of poly (I:C), a synthetic double-stranded RNA. The percentage of CD200+cells in the CK7+cell population (CD200+CK7+percentage) and the absolute number of these cells were determined with flow cytometry, using trophoblast cells collected at day 8.5 and day 13.5 of gestation. The potential effect of poly (I:C) on CD200 expression was also evaluated by detecting the CD200+CK7+percentage in trophoblast cells incubated in the presence or absence of poly (I:C),in vitro. The distribution pattern of CD200+cells at the feto–maternal interface was evaluated by immunocytochemical examination. When 104cells were analyzed at day 8.5 of gestation in each case, no significant difference was observed between the poly (I:C)-treated group and the control PBS group either in the CD200+CK7+percentage or in the absolute number of these cells. Similar results were observed both in BALB/c × C57BL/6 mice and in BALB/c × BALB/c mice. However, the CD200+CK7+percentage was significantly decreased in the poly (I:C)-treated group when evaluated at day 13.5 of gestation. Accordingly, a dramatically elevated rate of embryo resorption was observed at this time point of pregnancy after the administration of poly (I:C). In addition, the CD200+CK7+percentage was significantly lower in trophoblast cells incubated with poly (I:C) at a certain concentration,in vitro, while histocytochemical examination showed the CD200+cells mainly scattered in placental tissue adjacent to the interface of the placenta and uterus. This indicates that sufficient expression of the CD200 molecule on CK7+cells at the feto–maternal interface may be necessary for the maintenance of embryos during pregnancy in this rodent model, while poly (I:C) administration may increase embryo resorption, at least partially via direct inhibition of CD200 expression on CK7+cells.