Nadeau-Vallée Mathieu, Obari Dima, Palacios Julia, Brien Marie-Ève, Duval Cyntia, Chemtob Sylvain, Girard Sylvie
Departments of PediatricsOphthalmology and Pharmacology, CHU Sainte-Justine Research Center, Montreal, Quebec, Canada.
Department of PharmacologyUniversité de Montréal, Montreal, Quebec, Canada.
Reproduction. 2016 Dec;152(6):R277-R292. doi: 10.1530/REP-16-0453. Epub 2016 Sep 27.
Inflammation is essential for successful embryo implantation, pregnancy maintenance and delivery. In the last decade, important advances have been made in regard to endogenous, and therefore non-infectious, initiators of inflammation, which can act through the same receptors as pathogens. These molecules are referred to as damage-associated molecular patterns (DAMPs), and their involvement in reproduction has only recently been unraveled. Even though inflammation is necessary for successful reproduction, untimely activation of inflammatory processes can have devastating effect on pregnancy outcomes. Many DAMPs, such as uric acid, high-mobility group box 1 (HMGB1), interleukin (IL)-1 and cell-free fetal DNA, have been associated with pregnancy complications, such as miscarriages, preeclampsia and preterm birth in preclinical models and in humans. However, the specific contribution of alarmins to these conditions is still under debate, as currently there is lack of information on their mechanism of action. In this review, we discuss the role of sterile inflammation in reproduction, including early implantation and pregnancy complications. Particularly, we focus on major alarmins vastly implicated in numerous sterile inflammatory processes, such as uric acid, HMGB1, IL-1α and cell-free DNA (especially that of fetal origin) while giving an overview of the potential role of other candidate alarmins.
炎症对于胚胎成功着床、维持妊娠及分娩至关重要。在过去十年中，关于内源性（即非感染性）炎症引发因子取得了重要进展，这些引发因子可通过与病原体相同的受体发挥作用。这些分子被称为损伤相关分子模式（DAMPs），它们在生殖中的作用直到最近才被揭示。尽管炎症对于成功生殖是必要的，但炎症过程的过早激活会对妊娠结局产生毁灭性影响。许多DAMPs，如尿酸、高迁移率族蛋白B1（HMGB1）、白细胞介素（IL）-1和游离胎儿DNA，在临床前模型和人类中都与妊娠并发症相关，如流产、先兆子痫和早产。然而，警报素对这些情况的具体作用仍存在争议，因为目前缺乏关于其作用机制的信息。在这篇综述中，我们讨论了无菌性炎症在生殖中的作用，包括早期着床和妊娠并发症。特别地，我们重点关注了大量参与众多无菌性炎症过程的主要警报素，如尿酸、HMGB1、IL-1α和游离DNA（尤其是胎儿来源的），同时概述了其他候选警报素的潜在作用。
