Sterile inflammation and pregnancy complications: a review.
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.
Departments of PediatricsOphthalmology and Pharmacology, CHU Sainte-Justine Research Center, Montreal, Quebec, Canada.|Department of PharmacologyUniversité de Montréal, Montreal, Quebec, Canada.
Mathieu
M
Nadeau-Vallée
Department of PharmacologyUniversité de Montréal, Montreal, Quebec, Canada.
Dima
D
Obari
Department of Obstetrics & GynecologyCHU Sainte-Justine Research Center, Montreal, Quebec, Canada.
Julia
J
Palacios
Department of Obstetrics & GynecologyCHU Sainte-Justine Research Center, Montreal, Quebec, Canada.|Department of MicrobiologyVirology and Immunology, Université de Montréal, Montreal, Quebec, Canada.
Marie-Ève
MÈ
Brien
Department of Obstetrics & GynecologyCHU Sainte-Justine Research Center, Montreal, Quebec, Canada.
Cyntia
C
Duval
Departments of PediatricsOphthalmology and Pharmacology, CHU Sainte-Justine Research Center, Montreal, Quebec, Canada sylvie.girard@recherche-ste-justine.qc.ca.|Department of PharmacologyUniversité de Montréal, Montreal, Quebec, Canada.
Sylvain
S
Chemtob
Department of PharmacologyUniversité de Montréal, Montreal, Quebec, Canada sylvie.girard@recherche-ste-justine.qc.ca.|Department of Obstetrics & GynecologyCHU Sainte-Justine Research Center, Montreal, Quebec, Canada.|Department of MicrobiologyVirology and Immunology, Université de Montréal, Montreal, Quebec, Canada.
Sylvie
S
Girard
D005260:Female; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000503:physiopathology*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology*