About 1 in 10 pregnancies have problems with the placenta, which means the fetus isn’t getting enough of the oxygen and nutrients it needs to grow. Now researchers at Duke University School of Medicine have discovered that a particular protein, PIEZO1, plays a crucial role in helping the placenta develop normally.
Learning more about PIEZO1 and how it helps the placenta form could help detect pregnancy problems earlier and pave the way to preventing unexplained miscarriages, preeclampsia, or fetal growth restriction.
“We show that PIEZO1 acts as a sensor that detects mechanical forces like stretch or pressure and turns them into a chemical signal that tells cells it’s time to fuse,” said Huanghe Yang, PhD, associate professor of biochemistry and senior author of the study. “This process is essential for placenta formation. Without PIEZO1, this fusion process fails, the placenta doesn’t form properly, and embryos in mouse models do not survive.”
The results were published July 2025 in Nature Communications.
The discovery could also lead to better understanding of other body processes that involve cell fusion, including bone repair, cancer progression, or viral infections. “Mechanical forces shape how all tissues and organs develop. The fusion mechanism we uncovered has broader implications in other areas of biology,” Yang said.
The 2021 Nobel Prize winners in Physiology or Medicine demonstrated that PIEZO1 helps cells sense touch or pressure. PIEZO1 has also been shown to support blood vessel development during pregnancy. Yang’s new study reveals the protein’s role in helping build the placenta itself.
Using human placental cells, mice, and cell lines, Yang’s team found that PIEZO1 is active in placental cells called trophoblasts. “These trophoblasts must fuse together to form the syncytiotrophoblast, a vital outer layer that allows nutrients and oxygen to pass from mother to baby without leakage,” Yang said.
“For the first time, we show that PIEZO1 senses mechanical forces in these cells and helps trigger the fusion process by allowing calcium to enter the cell.” The calcium activates another protein, TMEM16F, which sends a signal telling neighboring cells to fuse.
Next, Yang’s lab is exploring if PIEZO1 gene mutations in humans lead to pregnancy complications and whether drugs could be developed to enhance or restore PIEZO1 activity. “These next steps will help us move from a basic scientific discovery toward tools and treatments that could improve pregnancy outcomes,” he said.
Other authors of the study, all at Duke, are postdoctoral associate Yang Zhang, PhD, doctoral student Ke Z. Shan, and research associate Pengfei Liang, PhD (co-first authors); doctoral student Augustus J. Lowry; and Liping Feng, MD, associate professor of obstetrics and gynecology.
The study was funded by National Institutes of Health grants R35GM153196 and DP2GM126898.