Premature birth, prolonged labor influenced by progesterone balance

Press release

Thursday 11 March 2021

New research in mice sheds light on hormonal regulation needed in late pregnancy and paves the way for therapy.

New research from the National Institutes of Health has found that imbalanced progesterone signals can cause some pregnant women to experience preterm or prolonged labor. The mouse study – published online in the Proceedings of the National Academy of Sciences – provides new insights into the development of treatments.

During pregnancy, the hormone progesterone helps prevent the uterus from contracting and starting labor prematurely. This occurs through molecular signaling involving types of progesterone receptors A and B, called PGR-A and PGR-B. In this one-of-a-kind study, scientists showed how unbalanced PGR-A and PGR-B signaling can affect the length of pregnancy.

“We used genetically engineered mouse models to alter the ratio of PGR-A and PGR-B in the muscle compartment of the uterus called the myometrium,” said lead author Francesco DeMayo, Ph.D., director of the National Institute of the Environment. Reproductive Biology and Developmental Health Sciences Laboratory. “Our team discovered that PGR-A promotes muscle contraction and PGR-B prevents such contraction, and we have identified the biological pathways influenced by both forms.”

Previous research has shown that PGR-A regulates the processes involved in the induction of childbirth and that PGR-B affects molecular pathways related to maintaining the normal course of pregnancy. This study builds on these results, revealing that the relative abundance of PGR-A and PGR-B may be essential for promoting a healthy pregnancy. The implications for public health are significant.

Premature birth affects 10% of all pregnancies and is the leading cause of neonatal morbidity and mortality worldwide, while prolonged labor increases the risk of infection, uterine rupture and neonatal distress, the researchers say.

Scientists have pointed out that care for preterm births can come with high social and economic costs, with infants born prematurely being at greater risk of suffering from conditions ranging from blindness to cerebral palsy. Prolonged labor can harm both mother and infant and lead to a cesarean section.

Progesterone therapy to prevent preterm labor may help a subset of patients, but for others, confounding factors may reduce effectiveness, noted Steve Wu, Ph.D., lead author of the study and scientist of DeMayo’s laboratory. Wu said the research team found new molecules that control uterine muscle contraction and that they could serve as future therapeutic targets. He added that the current study could also help advance treatment for obstructed labor – the clinical name for abnormally slow or prolonged labor.

“Although stimulation of labor by oxytocin infusion is an approved measure to alleviate obstructed labor, serious side effects have been associated with this treatment,” Wu said. “New proteins that we have identified as part of the treatment. of progesterone signaling could serve as a key molecular switch in uterine contraction, through drug regulation of their activities, ”he explained.

“Hormonal signaling during pregnancy is complicated and involves both hormonal levels and the types of receptors in the womb that detect hormones,” said co-lead author Mary Peavey, MD, of the Department of Obstetrics and of Gynecology at the University of North Carolina. at Chapel Hill. “This publication sheds light on how hormones influence labor and therefore can be used to help women when the uterus goes into labor too early or for an extended period.”

This press release describes a basic research result. Basic research is improving our understanding of human behavior and biology, which is essential for advancing new and better ways to prevent, diagnose and treat disease. Science is an unpredictable and gradual process – every breakthrough in research builds on past discoveries, often in unexpected ways. Most clinical progress would not be possible without knowledge of basic basic research. To learn more about basic research, visit https://www.nih.gov/news-events/basic-research-digital-media-kit.

About the National Institute for Environmental Health Sciences (NIEHS): The NIEHS supports research to understand the effects of the environment on human health and is part of the National Institutes of Health. For more information on the NIEHS or on topics related to environmental health, visit https://www.niehs.nih.gov/ or subscribe to a news list.

About the National Institutes of Health (NIH):NIH, the country’s medical research agency, comprises 27 institutes and centers and is part of the US Department of Health and Human Services. The NIH is the principal federal agency that conducts and supports basic, clinical, and translational medical research, and studies the causes, treatments, and cures for common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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