UC San Francisco scientists announced on April 9 that they have mapped the biological connection between a pregnant woman and her developing baby in unprecedented detail, offering new insights into conditions such as preeclampsia, preterm birth, and miscarriage.
The research is significant because it helps clarify how healthy pregnancies develop and why complications may arise. By analyzing about 200,000 individual cells with advanced single-cell and spatial tools, the team compared these with nearly one million cells in their original positions within uterine and placental tissue. This allowed them to identify different cell types, track their development, and link them to pregnancy complications.
“This work gives us a much clearer picture of this critical region than ever before,” said Jingjing Li, Ph.D., associate professor in UCSF’s Department of Neurology and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research. He is the senior author of the study published in Nature on April 8.
The maternal-fetal interface is a temporary but essential structure composed of uterine and placental cells that forms about a week after fertilization. It supports fetal growth while maintaining the mother’s health. Its complexity has made it difficult for scientists to study both normal development during pregnancy as well as causes for complications. “By examining this tissue cell by cell across pregnancy, we can begin to understand both normal development and what may go wrong,” said Susan J. Fisher, Ph.D., professor of Obstetrics, Gynecology and Reproductive Sciences at UCSF.
One key finding was the discovery of a previously unknown maternal cell type located where fetal placental cells first enter the uterus. These cells appear to regulate how deeply placental cells invade uterine tissue—a process crucial for establishing blood flow to the fetus—and were found to carry cannabinoid receptors that allow cannabis molecules to latch onto them. The researchers observed that exposure to cannabinoid molecules further restricted placental invasion by these cells. “Population studies have linked cannabis use during pregnancy to poorer outcomes,” said Cheng Wang, Ph.D., first author of the study. “This cell type may help explain the biological basis of that association.”
The team also integrated genetic data from more than 10,000 patients in order to map risk signals for conditions including preterm birth, preeclampsia, and miscarriage onto regulatory regions controlling gene activity. They found that certain cell types involved in remodeling uterine blood vessels are most affected in cases of preeclampsia—a potentially life-threatening disorder marked by sudden high blood pressure—suggesting disrupted communication between maternal and fetal cells may be responsible.
Having established this detailed cellular map from healthy pregnancies, researchers plan next steps studying complicated pregnancies with hopes for identifying potential treatment targets.
