The most detailed map yet of the maternal–fetal connection
Advanced single-cell and spatial methods reveal the maternal–fetal connection in unprecedented detail.
Researchers from University of California San Francisco (UCSF; CA, USA) have investigated the human maternal–fetal interface (MFI), constructing the most comprehensive cell atlas of the connection to date. This work not only illuminates new cell types and healthy MFI development, but provides an insight into conditions such as preeclampsia, miscarriage and preterm birth.
The MFI is a temporary structure comprised of uterine and placental cells that is essential to both maternal and fetal health. Stymied by the MFI’s complexity, researchers in the past have struggled to study how healthy pregnancies develop and why complications arise. In their recent study, the UCSF team elected to use advanced single-cell and spatial tools to map MFI development throughout pregnancy and better understand the processes that underlie healthy development.
They conducted single-nucleus multiome profiling, spatial transcriptomics and multiplex protein imaging on snap-frozen MFI samples from placenta tissue banks at Stanford University (CA, USA) and UCSF. These samples were from healthy pregnancies aborted during the first and second trimesters. The study also included analysis of fresh placental samples, which were collected following term delivery. Both sample types excluded tissues displaying health abnormalities, allowing the team to create a cell atlas reflecting healthy development.
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This comprehensive cell atlas – documenting healthy MFI development from early gestation to term – revealed a previously unknown maternal cell type that regulates the establishment of placental cells within uterine tissue, an important process for ensuring blood flow to the fetus. Furthermore, these cells were shown to have a cannabinoid receptor that, when exposed to cannabinoid molecules, caused the cells to restrict placental cell establishment, offering a potential explanation for poorer outcomes associated with cannabis use during pregnancy.
By integrating genetic data from over 10,000 patients, the team was able to identify specific cell types and states that strongly associate with conditions like preeclampsia, miscarriage and preterm birth. They found that the cell types involved in uterine blood vessel remodeling were the most affected during preeclampsia, a disorder characterized by sudden high blood pressure.
Although this study conducted extensive cell profiling, the team is sure that there are more cell states and subtypes associated with normal pregnancy and pathological deviations to be discovered with further spatial and temporal investigations. The multimodal healthy MFI atlas presented in this study serves as a strong base upon which this work can build, including more research into complicated pregnancies and their potential therapeutic targets.