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San Francisco, CA — In a breakthrough study, researchers at UC San Francisco have uncovered a molecular mechanism that could explain the timing of birth, shedding new light on the mystery of preterm labor. Published in the journal Cell on January 21, the research identifies a “molecular timer” in mice that begins its countdown at the earliest stages of pregnancy. If similar mechanisms are found in humans, the discovery could pave the way for innovative tests and interventions to prevent preterm births.
A full-term human pregnancy typically lasts 40 weeks, but normal pregnancies can vary from 38 to 42 weeks. Preterm births, occurring before 37 weeks, affect 10% of all pregnancies worldwide, often leading to serious complications for newborns. Despite its prevalence, the mechanisms driving preterm birth have long eluded scientists.
“Preterm birth is a huge problem around the world, and for a long time, nobody has really understood it,” said senior author Dr. Adrian Erlebacher, MD, Ph.D., a professor of laboratory medicine at UCSF. “We hope our work can start to shed light on the underlying mechanism.”
DNA Packaging and Labor Onset
The UCSF team focused on a protein called KDM6B, which plays a critical role in regulating gene activity by modifying histones—proteins that package DNA within cells. KDM6B removes methyl groups from histones, allowing DNA to become accessible and activating genes crucial for pregnancy and labor.
The researchers found that when KDM6B was inhibited in mice, pregnancy lasted longer, delaying labor. Initially, they believed KDM6B activated genes in epithelial cells in late pregnancy. However, further analysis revealed that KDM6B affects fibroblasts—structural cells not previously associated with labor regulation—during the first days of pregnancy.
“This wasn’t something we anticipated, and it completely reshaped our understanding of the cell types and processes driving labor onset,” said Dr. Tara McIntyre, Ph.D., the study’s lead author.
The Molecular Timer: How It Works
Shortly after conception, histones in uterine fibroblasts gain methyl groups, keeping specific genes inactive to maintain pregnancy. Over time, these methyl groups erode at a steady rate, eventually allowing labor-related genes to activate. This gradual process functions as a timer for pregnancy length.
“When histone methylation erodes enough, nearby genes flip on,” Erlebacher explained. “This timer essentially starts ticking right at the beginning of pregnancy.”
Blocking KDM6B disrupted this process, causing excessive methylation and delaying gene activation, which led to prolonged pregnancies in mice.
Implications for Preterm Birth Research
The findings could have profound implications for human pregnancies. Researchers hypothesize that disruptions in this molecular timer might underlie some cases of preterm birth. For example, women with abnormally low histone methylation at the start of pregnancy might experience premature erosion, triggering labor-related genes too soon.
“Most research on preterm birth has focused on events immediately before labor,” Erlebacher noted. “Our results suggest that much earlier stages of pregnancy could be critical.”
If these molecular processes are found to play a similar role in humans, they could inform new diagnostic tools to identify women at risk for preterm labor and treatments to extend pregnancy safely.
The Road Ahead
While the study was conducted in mice, the next steps involve exploring whether the same molecular signals exist in humans. The researchers hope their findings will inspire further studies to understand and mitigate the risk of preterm birth, offering hope for healthier outcomes for mothers and babies worldwide.
For more information, see the original study: KDM6B-dependent epigenetic programming of uterine fibroblasts in early pregnancy regulates parturition timing in mice (Cell, 2025).
