The placenta plays an essential role in supporting the growth and development of the fetus. Specialised
trophoblast cells cover the surface of this organ, a subset of which also invade into the maternal endometrium
remodelling the uterine spiral arteries to provide efficient blood flow to the developing feto-placental unit.
Interaction of maternal immune cells with the trophoblast aids both placental development and function, and
maternal immunotolerance to the semi-allogenic feto-placental unit. This includes circulating immune cells,
immune cells resident in the decidua and placental macrophages. Dysfunction in immune cell-trophoblast
interactions is associated with complications of pregnancy including preeclampsia, fetal growth restriction and
preterm birth. However, we still have very little knowledge about the exact mechanism behind these
interactions, in both health and disease. A new research field has opened up in recent years, focused on the
role of exosomes (a type of extracellular vesicle) in cell-cell communication. Exosomes can be taken up by
recipient cells, resulting in a wide range of responses, including interaction with cell-surface receptors to
activate intracellular signalling cascades, and intracellular protein/miRNA functioning in recipient cells. It is well
established that trophoblast cells release exosomes into the mother’s bloodstream, enabling communication
with her immune cells. However, we have recently demonstrated that that this communication is a two-way
process; that a) exosomes released by maternal macrophages traffic to trophoblast; and b) macrophage
exosomes induce trophoblast cytokine responses. Thus, we hypothesize exosomes facilitate two-way dialogue
between the maternal immune system and the trophoblast, which modifies trophoblast function. This could
have huge implications for our understanding of regulation of trophoblast differentiation and function,
particularly through transfer of functional protein and miRNA exosome cargoes. We have established a
multidisciplinary group which encompasses specific expertise in maternal/fetal health, trophoblast immunology,
placental macrophage biology, exosome biology and omics analysis. Using a range of primary human
tissue/cells from across gestation, our primary objectives are to: 1) investigate trafficking of
monocyte/macrophage exosomes, and their cargo, to trophoblast; 2) determine the functional impact of these
exosomes on trophoblast differentiation and function in the context of normal pregnancy, and in maternal
inflammation; 3) determine the role of specific exosome proteins and miRNAs in exosome-mediated
trophoblast differentiation and function. Our findings will broaden our understanding of how maternal immune
cells interact with trophoblast cells. We will contribute knowledge as to how trophoblast differentiation and
function is regulated by interactions with maternal and placental immune cells, and how dysregulation of this
interaction may result in perturbation of normal trophoblast differentiation and function, contributing to
pregnancy complications.