分娩启动前后孕激素调控子宫肌层静息与收缩分子机制研究进展

Molecular regulation of progesterone in myometrial contractility before and after parturition

雌性哺乳动物卵巢/胎盘产生的类固醇激素孕酮(P4)在维持妊娠和分娩中起着至关重要的作用。在妊娠期间孕酮(P4)通过阻断促炎症反应途径和抑制肌肉收缩相关蛋白基因(CAP)的表达,在维持子宫肌层静息中起主导作用。该作用主要通过P4与其受体(PR)结合后,在不同促炎性基因(如NF-κB、AP-1)以及CAP基因(如CX43等)启动子上招募共抑制子来实现。其中,还包括上调促炎性转录因子激活抑制剂(IkBa、MKP-1)和诱导CAP基因转录抑制因子(如ZEB1)等途径。当发生早产或胎儿足月时,P4/PR出现功能性阻断,引发PR-A亚型和P4代谢酶的表达增加,炎性转录因子(如NF-κB、AP-1)激活及PR协同激活因子的表达使其和共抑制子急剧减少等一系列分子事件,通过促进子宫肌层向高度协调的收缩单位转化从而引起分娩。本文详细综述了妊娠期间P4/PR通过不同途径维持子宫肌层静息的主要机制,分析了P4/PR功能性阻断引起子宫肌层收缩并最终导致分娩的主要因素。为进一步了解哺乳动物分娩启动的分子机制,更精准控制生产性动物分娩时间提供有益的参考。

The steroid hormones progesterone(P4),produced by the placenta in majority female mammals,plays crucial roles in the maintenance of pregnancy and the initiation of parturition.During pregnancy,P4 produced serves a dominant role in maintaining myometrial quiescence by blocking proinflammatory response pathways and inhibiting expression of“contractile”(contraction-associated protein,CAP)genes.Those effect was mainly achieved by binding to its receptor(PR)and recruiting co-repressors on the promoters of different proinflammatory genes(such as NF-κB,AP-1)and CAP genes(such as CX43,etc.).Near term or preterm labor occurs,with a functional progesterone withdrawaling,which leads to increase of PR-A and P4 metabolizing enzyme,activation of inflammatory transcription factors(such as NF-κB,AP-1)and sharp decrease of PR coactivator expression.Those series of molecular events promote uterine myometrium transformation to a highly coordinated contractile unit culminating in labor.In this article,we reviewed the mechanism of P4/PR maintaining myometrial quiescence through different ways during pregnancy and analyzed the main factors influencing functional P4/PR withdrawaling activation myometrial contractility ultimately leading to labor.It Provides a useful reference for further understanding the molecular mechanism of parturition initiation and more accurate control of the delivering time in domestic animal.