Bi-directional communication between monocytes and trophoblasts under hypoxia and hypoxia-reperfusion conditions

IntroductionPregnancy-related disorders such as preeclampsia are associated with syncytiotrophoblast (STB) stress and monocyte dysregulation. It remains unclear whether this stress derives from prolonged placental hypoxia or a hypoxia-reperfusion-type injury. Thus, this study investigated how these two models of STB stress impact trophoblast-monocyte interactions. MethodCobalt chloride chemically induced hypoxia in BeWo b30 cells. A transwell coculture system was used to examine trophoblast-monocyte signaling. qPCR quantified gene expression changes following coculture. Monocyte phagocytosis of E. Coli or adhesion to placental cells was determined via flow cytometry. Monocyte migration to placental signals was quantified using a cell counter. ResultsCobalt chloride induced a hypoxic state in BeWo b30s. Reperfusion restored the expression of indirect hypoxia genes and ER stress genes. Coculturing THP-1 monocytes with normoxic, hypoxic, and hypoxic-reperfused BeWo b30s promoted b30 survival but not wound-healing capacity. Compared to hypoxic-reperfused BeWos, hypoxic cells increased monocyte adhesion and inflammatory gene expression, decreased monocyte phagocytosis, and did not change monocyte migration. Finally, placental signaling in early-onset PE decreased monocyte chemotaxis, but monocyte precondition more strongly influenced migration compared to placental state. DiscussionOverall, hypoxic placental signals most effectively recapitulate monocyte functional behavior observed in preeclampsia. Further research is needed to understand spatial and temporal changes in monocyte-trophoblast interactions and pregnancy outcomes. Monocyte chemotaxis to primary placental signals varied by gestational age, maternal diagnosis, and monocyte condition, implying monocytes could be used as functional biomarkers to predict their behavior at the maternal-fetal interface as well as the onset of disease. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=79 SRC="FIGDIR/small/558721v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@15dae34org.highwire.dtl.DTLVardef@157dec7org.highwire.dtl.DTLVardef@1e2db81org.highwire.dtl.DTLVardef@b90ab6_HPS_FORMAT_FIGEXP M_FIG C_FIG