Macrophage efferocytosis in pregnancy and pregnancy complications.

abstractEfferocytosis is a vital process during early placental development that removes apoptotic cells generated through decidualisation and controls inflammation. As pregnancy progresses and levels of apoptotic placental cells increase, macrophage efferocytosis remains essential to maintain a healthy pregnancy. There is mounting evidence that dysfunctional macrophage efferocytosis is implicated in the pathogenesis of multiple pregnancy complications. This includes disorders of malplacentation, such as preeclampsia and fetal growth restriction, wherein impaired spiral artery remodelling and inflammation in the decidua impair placental vascularisation leading to maternal hypertension, or impaired fetal growth. As a shift in macrophage phenotype and cytokine secretion is required for the onset of labour, alterations in phenotype earlier in pregnancy may be associated with preterm birth. In rarer pregnancy complications, such as chronic histiocytic intervillositis, impaired efferocytosis and wound healing by infiltrating intervillous, macrophages may contribute to their excessive recruitment into the intervillous space, hindering placental function. In this review, we describe the importance of efferocytosis by various maternal macrophage populations in the placenta and review the evidence of how impaired efferocytosis contributes to pathology. Furthermore, therapeutic targeting of macrophage efferocytosis and how this may be used to prevent or treat obstetric conditions are explored. LAY SUMMARY: During pregnancy, the body must safely clear away any dead cells in the womb to allow the placenta to grow and develop properly. This clean-up process is called efferocytosis, and it is carried out by immune cells known as macrophages. By removing these dying cells, macrophages help prevent inflammation and create the right environment for a healthy pregnancy. When efferocytosis does not work as it should, it can contribute to pregnancy complications. For example, if dead cells are not removed, the mother may develop high blood pressure, or the baby may not grow as expected. In rare pregnancy conditions, too many macrophages build up in the placenta. This build-up can interfere with the placenta's ability to support the baby and can lead to stillbirth. In this review, we discuss why macrophage efferocytosis is so important for normal placental development and explore how problems in this process may lead to disease. We also consider new treatment ideas that could help control how macrophages work to prevent or manage pregnancy complications.