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Preterm Birth, Prolonged Labor Influenced by Progesterone Balance

Novel research in mice sheds light on hormone regulation needed in late pregnancy, opens door for therapy.

pregnant woman holding her hand on stomach and back

Care for preterm deliveries can result in high social and economic costs, with infants experiencing disorders ranging from blindness to cerebral palsy, according to the researchers. Prolonged labor can harm the mother’s health and lead to cesarean delivery.
(Photo courtesy of Prostock-studio / Shutterstock.com)

New research by the National Institutes of Health found that unbalanced progesterone signals may cause some pregnant women to experience preterm labor or prolonged labor. The study in mice — published online in the Proceedings of the National Academy of Sciences — provides novel insights for developing treatments.

During pregnancy, the hormone progesterone helps to prevent the uterus from contracting and going into labor prematurely. This occurs through molecular signaling involving progesterone receptor types A and B, referred to as PGR-A and PGR-B. In this first-of-its-kind study, the scientists showed how unbalanced PGR-A and PGR-B signaling can affect pregnancy duration.

“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 senior author Francesco DeMayo, Ph.D., head of the National Institute of Environmental Health Sciences Reproductive and Developmental Biology Laboratory. “Our team found that PGR-A promotes muscle contraction and PGR-B prevents such contraction, and we identified the biological pathways influenced by both forms.”

Previous research showed that PGR-A regulates processes involved in initiating childbirth and that PGR-B affects molecular pathways related to maintaining the normal course of pregnancy. This study builds on those findings, revealing that the relative abundance of PGR-A and PGR-B may be critical in promoting healthy pregnancy. The public health implications are significant.

Preterm birth affects 10% of all pregnancies and is the primary cause of neonatal morbidity and mortality worldwide, while prolonged labor increases the risks of infection, uterine rupture, and neonatal distress, according to the researchers.

The scientists pointed out that care for preterm deliveries can result in high social and economic costs, with infants born preterm at greater risk for experiencing disorders ranging from blindness to cerebral palsy. Prolonged labor can harm both mother and infant and lead to cesarean delivery.

Progesterone treatment aimed at preventing premature labor can help a subset of patients, but for other individuals, confounding factors may reduce effectiveness, noted Steve Wu, Ph.D., first author on the study and a staff scientist in DeMayo’s lab. Wu said that the research team found novel molecules that control uterine muscle contraction, and they could serve as future therapeutic targets. He added that the current study also may help to advance treatment for labor dystocia — the clinical name for abnormally slow or protracted labor.

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

“Hormone signaling in pregnancy is complicated and involves both the hormone levels and the types of receptors in the uterus that sense the hormones,” said co-first author Mary Peavey, M.D., from the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. “This publication sheds light on how hormones influence labor and can thus be used to help women when the uterus goes into labor too soon or for a prolonged period.”

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Reference: Peavey MC, Wu SP, Li R, Liu J, Emery OM, Wang Tianjuan, Zhou Lecong, Wetendorff M, Yallampalli C, Gibbons WE, Lydon JP, DeMayo FJ. 2021. Progesterone receptor isoform B regulates the Oxtr-Plcl2-Trpc3 pathway to suppress uterine contractility. Proc Natl Acad Sci USA: doi: 10.1073/pnas.2011643118 [Online 11 March 2021].

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    傳統的遊樂場所往往受限於空間和設備，但線上娛樂城則打破了這一限制。從經典的賭場遊戲到最新的電子遊戲，娛樂城遊戲的種類繁多，滿足了不同玩家的需求。而且，這些遊戲還具有高度的互動性和真實感，使玩家仿佛置身於真實的遊樂場所。

    ### 線上娛樂城：安全與便利並存

    線上娛樂城的另一大優勢是其安全性。許多線上娛樂城都採用了先進的加密技術，確保玩家的資料和交易安全。此外，線上娛樂城還提供了多種支付方式，使玩家可以輕鬆地進行充值和提現。

    然而，選擇線上娛樂城時，玩家仍需謹慎。建議玩家選擇那些具有良好口碑和正規授權的娛樂城，以確保自己的權益。

    結語：

    娛樂城，無疑已經成為當代遊戲行業的一大趨勢。無論是娛樂城APP、娛樂城遊戲，還是線上娛樂城，都為玩家提供了前所未有的遊戲體驗。然而，選擇娛樂城時，玩家仍需保持警惕，確保自己的安全和權益。

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