human pregnancy: placental processes (Introduction)

by David Turell , Thursday, July 06, 2023, 18:36 (504 days ago) @ David Turell

First trimester specimens examined:

https://www.nature.com/articles/s41586-023-05869-0

"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 vessels1. Defects in trophoblast invasion and arterial transformation established during early pregnancy underlie common pregnancy disorders such as pre-eclampsia2. 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 organoids3,4 and trophoblast stem cells5. 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.

***

"Discussion:
Our systems biology approach has enabled us to explore potential interactions between EVTs and maternal decidual cells. First, we predict the ligand–receptor interactions between the maternal macrophages and EVT, in keeping with the importance of decidual innate immune cells for placentation32. We further explore the poorly described macrophage–EVT signalling axis in vitro and describe upregulation of motility genes in the EVT subsets. Second, we pinpoint the potential molecular and cellular mediators of arterial transformation during early pregnancy. Interactions between PV1-AOC3 and iEVT could drive iEVT tropism towards the arterial wall and mediate the destruction of arterial smooth muscle media. eEVTs have a specific ECM that could allow them to form the plug. There are also specific interactions with endothelial cells that enable eEVTs to adhere to them. These novel interactions add to our understanding of the communication between endothelial and eEVT cells. The effect of defective arterial transformation in the later stages of pregnancy is well-described and underpins the great obstetric syndromes9. Our study increases the understanding of these major pregnancy disorders, all of which have their origins in the first trimester. In addition, our roadmap of trophoblast differentiation can be used as a blueprint to design improved in vitro models that fully recapitulate the early stages of implantation."

Comment: the content of this very advanced study is too complex to include here. Cell to cell automatic interactions control the implantation and its subsequent functions. Obviously designed.