NLRP3 inflammasome: A new therapeutic target for high-risk reproductive disorders?

Abstract

The NOD-like receptor protein 3 (NLRP3) inflammasome is a key regulator of the host's immune response, and many immune and metabolic disorders are linked to its activation. This review aimed to investigate and clarify the relationship between this inflammasome and high-risk reproductive disorders. Papers cited here were retrieved from PubMed up to August 2020 using the keywords "NLRP3" or "NALP3", "caspase-1", "endometriosis", "gestational diabetes", "interleukin (IL)-18", "IL-1β", "pre-eclampsia (PE)", "preterm birth", "polycystic ovarian syndrome (PCOS)", "recurrent spontaneous abortion (RSA)", and combinations of these terms. The results show that NLRP3 inflammasome is associated with various high-risk reproductive disorders and many inflammatory factors are secreted during its activation, such as IL-1β induced during the development of endometriosis. PCOS is also associated with activation of the NLRP3 inflammasome, especially in overweight patients. It also participates in the pathogenesis of RSA and is activated in fetal membranes before preterm birth. The placentas of pregnant women with PE show higher expression of the NLRP3 inflammasome, and gestational diabetes mellitus occurs simultaneously with its activation. Current evidence suggest that the NLRP3 inflammasome plays an important role in female reproductive disorders. New treatment and management methods targeting it might help reduce the incidence of such disorders and improve neonatal outcomes.