Abstract

In preparation for delivery, the uterus transitions from actively maintaining quiescence during pregnancy to an active parturient state. This transition occurs as a result of the accumulation of pro-inflammatory signals which are amplified by positive feedback interactions involving paracrine and autocrine signaling at the level of each intrauterine cell and tissue. The amplification events occur in parallel until they reach a certain threshold, ‘tipping the scale’ and contributing to processes of uterine activation and functional progesterone withdrawal. The described signaling interactions all occur upstream from the presentation of clinical labor symptoms. In this review, we will: 1) describe the different physiological processes involved in uterine transition for each intrauterine tissue; 2) compare and contrast the current models of labor initiation; 3) introduce innovative models for measuring paracrine inflammatory interactions; and 4) discuss the therapeutic value in identifying and targeting key players in this crucial event for preterm birth.

Highlights

  • The uterus is a dynamic organ that regularly undergoes cyclic changes and irregularly experiences considerable change in form and function

  • While genes involved in immune/inflammatory regulation, protease/protease inhibitors, and cell adhesion categories were downregulated for labor in the mouse uterus, they were instead upregulated in human myometrium, suggesting a lesser contribution of progesterone withdrawal and a more abundant contribution of inflammation in human parturition (Bethin et al, 2003)

  • A follow-up study demonstrated that even without stretch, conditioned medium collected from cultured primary term myometrial cells or primary term decidual cells induced an upregulation of activation markers involved in adhesion and migration in early pregnant peripheral leukocytes, supporting a role for paracrine interactions between cell types in inducing leukocyte extravasation into gestational tissues (Farine et al, 2017)

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Summary

Introduction

The uterus is a dynamic organ that regularly undergoes cyclic changes and irregularly experiences considerable change in form and function. They hypothesize that human parturition occurs when pro-inflammatory mediators are upregulated and amplified until their signals exceed a threshold level that stimulates functional progesterone withdrawal and the other components required for the uterus to transition to its activated state for labor (Talati et al, 2017; Keelan, 2018).

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