Premature birth, prolonged birth influenced by progesterone balance

Press release

Thursday, March 11, 2021

New research in mice sheds light on the hormonal regulation needed at the end of pregnancy and opens the door to therapy.

New research from the National Institutes of Health found that unbalanced progesterone signals can cause some pregnant women to suffer from premature labor or prolonged labor. The study in mice, published online in the Proceedings of the National Academy of Sciences, provides news on the development of treatments.

During pregnancy, the hormone progesterone helps prevent the uterus from contracting and entering labor prematurely. This occurs through molecular signaling that includes type A and B progesterone receptors, known as PGR-A and PGR-B. In this first study of this type, scientists demonstrated how unbalanced PGR-A and PGR-B signaling can affect the duration of pregnancy.

“We used genetically modified mouse models to alter the proportion of PGR-A and PGR-B in the uterine muscle compartment, called the myometrium,” said the author, Francesco DeMayo, Ph.D., head of the ‘National Institute of the Environment. Laboratory of reproductive biology and the development of health sciences. “Our team found that PGR-A promotes muscle contraction and PGR-B prevents this 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 onset of labor and that PGR-B affects the molecular pathways related to maintaining the normal course of pregnancy. This study builds on these findings, revealing that the relative abundance of PGR-A and PGR-B may be critical to 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 risks of infection, uterine rupture and neonatal anxiety, according to the researchers.

Scientists noted that caring for premature birth can lead to high economic and social costs, as premature babies are at higher risk for disorders ranging from blindness to cerebral palsy. Prolonged labor can harm both the mother and the infant and can cause cesarean delivery.

Progesterone treatment aimed at preventing premature birth may help a subset of patients, but for other people, confounding factors may reduce efficacy, noted Steve Wu, Ph.D., lead author of the study. and DeMayo Wu’s lab scientist said the research team found new molecules that control uterine muscle contraction and could serve as future therapeutic targets. He added that the current study may also help advance the treatment of labor dystocia, the clinical name of abnormally slow or prolonged labor.

“Although stimulation of labor by oxytocin infusion is an approved measure to mitigate labor dystocia, serious side effects have been linked to this treatment,” Wu said. “The new proteins we identified as part of progesterone signaling could serve as a key molecular switch in uterine contraction, by regulating their drug-dependent activities,” he explained.

“Hormonal signaling during pregnancy is complicated and involves both hormone levels and the types of receptors in the uterus that detect hormones,” said co-author Mary Peavey, MD, of the University’s Department of Obstetrics and Gynecology. of North Carolina. and Chapel Hill. “This publication sheds light on how hormones influence childbirth and can therefore be used to help women when the uterus gives birth too soon or for an extended period of time.”

This press release describes a basic investigation. Basic research increases our understanding of human behavior and biology, which is critical to advancing new and better ways to prevent, diagnose, and treat disease. Science is an incremental and unpredictable process: every advance in research is based on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of basic basic research. For more information on basic research, visit https://www.nih.gov/news-events/basic-research-digital-media-kit.

About the National Institute of Environmental Health Sciences (NIEHS): 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 NIEHS or environmental health issues, visit https://www.niehs.nih.gov/ or subscribe to a news list.

Regarding the National Institutes of Health (NIH):
NIH, the country’s medical research agency, includes 27 institutes and centers and is a component of the U.S. Department of Health and Human Services. NIH is the leading federal agency that conducts and supports basic, clinical, and translational medical research and investigates 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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