Detailed cell mapping and ‘mini placentas’ give new insights into early human pregnancy over the entire placental development

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"... Understanding normal and disordered placentation at a molecular level can help answer questions about poorly understood disorders including miscarriage, stillbirth, and pre-eclampsia. ...

In the new study, scientists built on previous work investigating the early stages of pregnancy, to capture the process of placental development in unprecedented detail. Cutting-edge genomic techniques allowed them to see all of the cell types involved and how trophoblast cells communicate with the maternal uterine environment around them.

The team uncovered the full trajectory of trophoblast development, suggesting what could go wrong in disease and describing the involvement of multiple populations of cells, such as maternal immune and vascular cells. ..."

From the abstract:

"The relationship between the human placenta—the extraembryonic organ made by the fetus, and the decidua—the mucosal layer of the uterus, is essential to nurture and protect the fetus during pregnancy. Extravillous trophoblast cells (EVTs) derived from placental villi infiltrate the decidua, transforming the maternal arteries into high-conductance vessels. Defects in trophoblast invasion and arterial transformation established during early pregnancy underlie common pregnancy disorders such as pre-eclampsia. Here we have generated a spatially resolved multiomics single-cell atlas of the entire human maternal–fetal interface including the myometrium, which enables us to resolve the full trajectory of trophoblast differentiation. We have used this cellular map to infer the possible transcription factors mediating EVT invasion and show that they are preserved in in vitro models of EVT differentiation from primary trophoblast organoids and trophoblast stem cells. We define the transcriptomes of the final cell states of trophoblast invasion: placental bed giant cells (fused multinucleated EVTs) and endovascular EVTs (which form plugs inside the maternal arteries). We predict the cell–cell communication events contributing to trophoblast invasion and placental bed giant cell formation, and model the dual role of interstitial EVTs and endovascular EVTs in mediating arterial transformation during early pregnancy. Together, our data provide a comprehensive analysis of postimplantation trophoblast differentiation that can be used to inform the design of experimental models of the human placenta in early pregnancy."

Cell mapping and ‘mini placentas’ give new insights into human pregnancy | University of Cambridge Researchers have mapped the complete trajectory of placental development, helping shed new light on why pregnancy disorders happen.

Spatial multiomics map of trophoblast development in early pregnancy (open access)

Fig. 1: Trophoblast cell states in the early maternal–fetal interface