What sets off labour when a baby is ready to be delivered has long been a mystery, but now it seems that the immune system pulls the trigger. The uterus appears to start contracting after immune cells transfer energy to its muscle cells via tiny tubes. 聽
鈥淏y understanding all the steps along the road, we鈥檙e getting closer to identifying therapeutics for preventing preterm birth,鈥� says at Mount Sinai Hospital in Toronto, Canada.
Lye and his colleagues previously found that, towards the end of pregnancy, the human uterus into the bloodstream. These usher immune cells called monocytes from the blood into the uterus. The monocytes accumulate in the muscle tissue of the uterus and turn into other immune cells called macrophages.
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In the latest study, the team investigated the role of these macrophages by incubating them with muscle cells from uterus biopsies collected from pregnant women undergoing Caesarean sections at full term. 鈥淩emarkably, we found that the macrophages made these little tube-like structures that attached to the muscle cells,鈥� says Lye.
Even more remarkably, the researchers could see the macrophages sending mitochondria through these tiny tubes into the muscle cells. 鈥淚n the images we took, you can see tons and tons of these mitochondria passing into the muscle cells,鈥� says Lye.
Mitochondria are probably transferred to muscle cells in the uterus to give it enough energy to contract and push out the baby, says Lye. In line with this, the team found that levels of the energy-providing molecule adenosine triphosphate increased in the uterine muscle cells after the macrophages connected their mitochondria-delivering tubes to them.
The influx of mitochondria also increased levels of an enzyme that breaks down progesterone. This probably signals for labour to begin, because we know a drop in this hormone turns on the genes required for labour.
鈥淚n virtually all species, in order to go into labour, you have to get rid of progesterone,鈥� says Lye. 鈥淢ost species do this by stopping the production of progesterone, but in humans, progesterone levels in the circulation don鈥檛 fall by the time of labour. So for decades, people have been saying: 鈥榃hy is it that women actually go into labour?鈥欌�� he says. The new results suggest that human labour is specifically activated by a drop of progesterone in the muscle cells of the uterus, not the whole body, he says.
The researchers hope to use their findings to develop more effective interventions for preventing preterm births, which occur before 37 weeks of gestation. Being born before this time, when organs haven鈥檛 fully developed, increases the likelihood of conditions such as cerebral palsy, learning difficulties, asthma and vision and hearing problems. 聽聽聽
If you show signs of going into early labour, you can be given drugs called tocolytics that relax the uterus and stop contractions. However, these usually delay labour by only a few days.
Lye and his colleagues have already investigated a different kind of drug called a broad-spectrum chemokine inhibitor for preventing preterm birth. This is designed to stop the initial recruitment of monocyte immune cells by the uterus that kicks off the series of events leading to labour. , but hasn鈥檛 yet been tested in people.
The researchers are also conducting a study looking at various immune cells in the blood of those who present with possible signs of early labour, to see if they can identify who is really at risk of delivering.
In the future, it may be possible to do a blood test to tell if someone at full term is likely to go into labour soon, says Lye. 鈥淚 think all of these things will be possible if we can find a way to detect the activation of the monocytes.鈥�
bioRxiv
