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RHOA/ROCK信号通路在整个孕期子宫肌层各阶段调节中的作用。

The role of the RHOA/ROCK pathway in the regulation of myometrial stages throughout pregnancy.

作者信息

Carvajal Jorge A, Galaz Jose, Villagrán Sofía, Astudillo Rocío, Garmendia Liliana, Delpiano Ana María

机构信息

Departamento de Obstetricia, Escuela de Medicina, Unidad de Medicina Materno Fetal, Pontificia Universidad Católica de Chile, Santiago, Chile (All authors).

出版信息

AJOG Glob Rep. 2024 Sep 18;4(4):100394. doi: 10.1016/j.xagr.2024.100394. eCollection 2024 Nov.

Abstract

BACKGROUND

Controlling uterine contractile activity is essential to regulate the duration of pregnancy. During most of the pregnancy, the uterus does not contract (i.e., myometrial quiescence). The myometrium recovers its contractile phenotype at around 36 weeks (i.e., myometrial activation) through several mechanisms. The RHOA/ROCK pathway plays a vital role in facilitating muscular contractions by calcium sensitization in humans. Yet, the role of this pathway during different myometrial stages, including quiescence, has not been elucidated.

OBJECTIVE

we aimed to study the role of the RHOA/ROCK pathway in the regulation of the different myometrial stages throughout pregnancy. Specifically, we hypothesized that the inhibition of the components of the RHOA/ROCK pathway play an important role in maintaining uterine quiescence.

STUDY DESIGN

Myometrial samples were obtained from pregnant individuals who underwent cesarean section. Pregnant individuals who delivered preterm without labor (myometrial quiescence), preterm with labor (nonphysiological myometrial stimulation), term not in labor (activation), and term in labor (physiological myometrial stimulation) were included. The mRNA and protein expression of RHOA, ROCK I, ROCK II, RND1-3, and ROCK activity through pMYTP1 were evaluated.

RESULTS

We found that the human myometrium constitutively expressed RHOA/ROCK pathway components throughout pregnancy. No changes in the components of the RHOA/ROCK pathway were found during quiescence. Moreover, the RHOA protein and ROCK activity increased in the myometrium during labor, supporting the hypothesis that this pathway participates in maintaining the contractile activity of the myometrium. This study provides insight into the role of the RHOA/ROCK pathway in controlling myometrial contractile activity during pregnancy.

摘要

背景

控制子宫收缩活动对于调节孕期时长至关重要。在孕期的大部分时间里,子宫不会收缩(即子宫肌层静止)。子宫肌层在大约36周时通过多种机制恢复其收缩表型(即子宫肌层激活)。RHOA/ROCK通路在人类中通过钙敏化促进肌肉收缩方面起着至关重要的作用。然而,该通路在包括静止期在内的不同子宫肌层阶段中的作用尚未阐明。

目的

我们旨在研究RHOA/ROCK通路在整个孕期不同子宫肌层阶段调节中的作用。具体而言,我们假设抑制RHOA/ROCK通路的成分在维持子宫静止中起重要作用。

研究设计

从接受剖宫产的孕妇身上获取子宫肌层样本。纳入了未临产的早产孕妇(子宫肌层静止)、临产的早产孕妇(非生理性子宫肌层刺激)、未临产的足月孕妇(激活)和临产的足月孕妇(生理性子宫肌层刺激)。评估了RHOA、ROCK I、ROCK II、RND1 - 3的mRNA和蛋白表达以及通过pMYTP1评估的ROCK活性。

结果

我们发现人类子宫肌层在整个孕期都组成性表达RHOA/ROCK通路成分。在静止期未发现RHOA/ROCK通路成分的变化。此外,分娩期间子宫肌层中RHOA蛋白和ROCK活性增加,支持了该通路参与维持子宫肌层收缩活动的假设。这项研究为RHOA/ROCK通路在孕期控制子宫肌层收缩活动中的作用提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c48/11491706/7c00f89f6532/gr1.jpg

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