A spatially resolved timeline of the human maternal-fetal interface

Beginning in the first trimester, fetally-derived extravillous
trophoblasts (EVTs) invade the uterus and remodel its spiral arteries,
transforming them into large, dilated blood vessels. Several mechanisms
have been proposed to explain how EVTs coordinate with the maternal
decidua to promote a tissue microenvironment conducive to spiral artery
remodeling (SAR). However, it remains a matter of debate which immune and
stromal cells participate in these interactions and how this evolves with
respect to gestational age. Here, we used a multiomic approach combining
the strengths of spatial proteomics and transcriptomics to construct the
first spatiotemporal atlas of the human maternal-fetal interface in the
first half of pregnancy. We used multiplexed ion beam imaging by
time-of-flight (MIBI-TOF) and a 37-plex antibody panel to analyze ~500,000
cells and 588 arteries within intact decidua from 66 patients between 6-20
weeks of gestation, integrating this with coregistered transcriptomic
profiles. Gestational age substantially influenced the frequency of
maternal immune and stromal cells, with tolerogenic subsets expressing
CD206, CD163, TIM-3, Galectin-9, and IDO-1 increasingly enriched and
colocalized at later time points.  In contrast, SAR progression
preferentially correlated with EVT invasion and was transcriptionally
defined by 78 gene ontology pathways exhibiting unique monotonic and
biphasic trends.  Lastly, we developed an integrated model of SAR
where invasion is accompanied by upregulation of pro-angiogenic,
immunoregulatory EVT programs that promote interactions with vascular
endothelium while avoiding activation of maternal immune cells.