Premature babies are at high risk of neonatal and long-term health complications, and preventing women from giving birth early would prevent these problems. Although some risk factors are already known – diseases or infections in pregnancy, uterine disorders, smoking, inadequate diet, excessive physical exercise, stressful work activity, fetal malformation… – that are associated with preterm birth, a new one has now been identified. protein called Piezo1, which is responsible for regulating the behavior of the uterus and could be the cause of premature birth.
The Piezo1 protein keeps the uterus relaxed so it continues to stretch and expand throughout the 40 weeks of pregnancy as the fetus develops, suggests the new study, published in The Journal of Physiology. The discovery of Piezo1 in the uterus and its role in maintaining stretch-activation channels during pregnancy opens a new avenue for developing drugs and therapies that could prevent or delay preterm birth.
Professor Iain Buxton, from the Myometrium Research Group at the University of Nevada, explained that “pregnancy is the most impressive example of a human muscle undergoing mechanical stress for a prolonged period.” And he adds that “the finding of Piezo1 in the muscular layer of the uterus means that it is locally controlled and coordinated through a mechanism activated by stretching, and not by the hormonal influence of the ovaries or the placenta, as has been supposed”.
Potential pharmacological target to stop preterm labor
The outer muscular layer of the uterus is the only muscle that is not regulated by nerves and has to remain inactive throughout pregnancy despite the great expansion and stretching that occurs as the fetus grows. Researchers at the University of Nevada, Reno School of Medicine, in the United States, analyzed samples of smooth muscle tissue from the uterus to study mechanistic pathways that provide a better understanding of the dynamics that control the uterus, how pregnancy is maintained, and which maintains the state of muscle relaxation (quiescence) until the time of delivery.
In premature tissue, Piezo1 expression is significantly decreased (downregulated), which ‘turns off’ latent muscle signaling and causes the uterus to contract and go into labor
By stretching the tissue of the uterus, to mimic what happens during pregnancy, Piezo1 channels are activated, which promotes the flow of calcium molecules generating a signaling cascade that activates the enzyme nitric oxide synthase to produce the nitric oxide molecule . This Piezo1 cascade drives and maintains the dormant state of the uterus.
Piezo1 controls the uterus by acting in a dose-dependent manner, where channel activity is stimulated by the chemical Yoda1 and inhibited by a chemical called Dooku1. When Piezo1 is regulated, the uterus remains relaxed. However, in premature tissue, Piezo1 expression is significantly decreased (down-regulated), which ‘turns off’ latent muscle signaling and causes the uterus to contract and go into labor.
Buxton says it’s “worrying” that drugs that can slow preterm labor aren’t yet available. “Thanks to the discovery of Piezo proteins, responsible for the body’s response to mechanical force, and our research, we are closer to developing a treatment. Piezo1 and its relaxation mechanism provide us with a target that we could activate with drugs. We have to prove it with more studies and we hope to carry out clinical trials in the future”, he concludes.
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