Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada; Departments of Physiology and University of Toronto, Ontario, Canada; Obstetrics & Gynecology, University of Toronto, Ontario, Canada.
Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada.
Placenta. 2020 Mar;92:28-36. doi: 10.1016/j.placenta.2020.02.005. Epub 2020 Feb 4.
Term labour is a state of physiological inflammation orchestrated by multiple uterine tissues (both fetal and maternal). This physiological inflammation preceding and accompanying labour onset is characterized by an increase in cytokine and chemokine secretion by the fetal membranes, as well as uterine tissues (i.e., decidua and myometrium). Pro-inflammatory cytokines and chemokines activate circulating maternal peripheral leukocytes as well as the uterine vascular endothelium to permit leukocyte infiltration into the uterus. This inflammatory milieu, in the absence of infection, is required for the initiation of labour as the uterine-infiltrated leukocytes secrete matrix metalloproteinases to induce fetal membrane rupture and cervical ripening as well as various labour mediators, which promote contractions of the myometrium. Myometrial activation at term and the onset of labour contractions are directly related to the changes in the ovarian/placental hormone progesterone and its downstream mediators (i.e., the progesterone receptors, PRA/B), which are also critical for maintenance of pregnancy. Our recent data provides direct evidence in support of local and functional P4 withdrawal in the uterine muscle (myometrium) via the activator protein-1 (AP-1) mediated pathway. This review outlines known mechanisms regulating activation of human labour, including progesterone and cytokine signaling. Understanding of the molecular mechanism of myometrial activation and labour onset could facilitate the development of new therapeutics for high-risk pregnant women to prevent premature uterine activation and preterm birth.
足月分娩是一种由多种子宫组织（胎儿和母体）协调的生理炎症状态。这种伴随分娩开始的生理炎症以前，由胎儿膜以及子宫组织（即蜕膜和子宫肌层）分泌细胞因子和趋化因子为特征。促炎细胞因子和趋化因子激活循环母体外周白细胞和子宫血管内皮细胞，使白细胞浸润到子宫中。在没有感染的情况下，这种炎症环境是分娩开始所必需的，因为浸润到子宫的白细胞分泌基质金属蛋白酶，以诱导胎膜破裂和宫颈成熟，以及各种分娩介质，促进子宫肌层收缩。足月时的子宫肌层激活和分娩收缩的开始与卵巢/胎盘激素孕酮及其下游介质（即孕酮受体 PRA/B）的变化直接相关，这些介质对于维持妊娠也是至关重要的。我们最近的数据提供了直接证据，支持通过激活蛋白-1（AP-1）介导的途径在子宫肌层（子宫肌层）中局部和功能性地去除 P4。这篇综述概述了调节人类分娩激活的已知机制，包括孕酮和细胞因子信号。对子宫肌层激活和分娩开始的分子机制的理解可以促进为高危孕妇开发新的治疗方法，以预防早产和早产。
