Researchers at Scripps Research have discovered how the uterus senses physical forces during labor, using molecular sensors to coordinate contractions. The study identifies PIEZO1 and PIEZO2 channels that detect pressure and stretch, explaining why labor can stall if these are disrupted. Findings could improve treatments for pregnancy complications.
Childbirth relies on more than hormones; physical forces like stretching and pressure play a key role in triggering effective uterine contractions. A new study from Scripps Research, published in the journal Science, details how the uterus uses specialized sensors to respond to these forces at the molecular level.
The research highlights two ion channels: PIEZO1, found in the smooth muscle of the uterus, which senses rising pressure during contractions, and PIEZO2, located in sensory nerves around the cervix and vagina, which activates when tissues stretch as the baby moves. These sensors convert mechanical signals into electrical and chemical responses that synchronize muscle activity.
"As the fetus grows, the uterus expands dramatically, and those physical forces reach their peak during delivery," says senior author Ardem Patapoutian, a Howard Hughes Medical Institute Investigator at Scripps Research. "Our study shows that the body relies on special pressure sensors to interpret these cues and translate them into coordinated muscle activity."
Experiments on mouse models demonstrated the sensors' importance. When both PIEZO1 and PIEZO2 were removed, contractions weakened, and births were delayed, showing the systems normally compensate for each other. The sensors also regulate connexin 43, a protein forming gap junctions that link muscle cells for unified action.
"Connexin 43 is the wiring that allows all the muscle cells to act together," explains first author Yunxiao Zhang, a postdoctoral researcher in Patapoutian's lab. "When that connection weakens, contractions lose strength."
Human uterine tissue samples mirrored the mouse patterns, suggesting similar mechanisms in people. This aligns with observations that blocking sensory nerves, as in some epidurals, can prolong labor by reducing feedback that strengthens contractions.
The discovery points to future therapies, such as modulating PIEZO activity to prevent preterm labor or aid stalled deliveries. It also underscores how mechanical sensing integrates with hormonal controls, like progesterone, to time contractions precisely.
Patapoutian, who shared the 2021 Nobel Prize for discovering PIEZO channels, notes: "Childbirth is a process where coordination and timing are everything. We're now starting to understand how the uterus acts as both a muscle and a metronome to ensure that labor follows the body's own rhythm."
The study, titled "PIEZO channels link mechanical forces to uterine contractions in parturition," involved collaborators from Scripps Research, University of California San Diego, and Washington University School of Medicine.
