Imma Perfetto
Cosmos science journalist
A new study in mice has discovered a molecular “timer” that activates in the first days of pregnancy and ticks along during gestation to control when they give birth.
If it is also discovered to be relevant in humans, the findings could lead to new tests to identify people who are at risk of preterm labour, allowing interventions to delay it.
“Preterm birth is a huge problem around the world, and for a long time nobody has really understood it,” says Adrian Erlebacher, professor of laboratory medicine at the University of California, San Francisco, and corresponding author of the new Cell paper.
“We hope our work can start to shed light on the underlying mechanism. The new findings raise the possibility that preterm birth is triggered by things that happen much earlier in pregnancy than we expected.”
In humans and mice, it’s been unclear whether birth is scheduled by a continuous process that happens throughout gestation, or whether it is triggered by signals released towards the end of foetal growth and development.
Erlebacher and his team have now found that a protein in fibroblast cells of the uterus regulates pregnancy length in mice. When they blocked the function of this protein, called KDM6B, mice gave birth later than usual.
The protein removes methyl chemical groups from proteins known as histones, which act like spools for DNA to wind around. Removing methyl chemical groups makes the DNA more accessible, allowing nearby genes to be switched on.
Experiments showed that shortly after conception, lots of methyl groups appear on histones near certain genes in uterine fibroblasts. These genes remain inactive to allow the uterus to support pregnancy.
The methylation levels on these histones fades in a slow and steady way over the course of pregnancy. Eventually, it decreases enough that nearby genes related to pregnancy events like labour are activated.
This histone methylation erosion, which involves but does not solely require KDM6B, functions as a pregnancy timer.
“Essentially what appears to happen is this timer gets wound up right at the beginning of pregnancy, and then progressively winds down,” Erlebacher says.
When they blocked KDM6B activity, histones near certain genes accumulated too much methylation early in pregnancy. This meant that, despite erosion, the genes were not activated on time and labour was delayed.
“The big question is whether these same processes are relevant in humans,” Erlebacher says. If the molecular signals are also disrupted in humans, the team thinks they could be linked to risk of preterm birth.
“If they are, then can we use them to predict or control pregnancy length?” asks Erlebacher.
