The Role of the NLRP3 Inflammasome in the Molecular and Biochemical Mechanisms of Cervical Ripening: A Comprehensive Review

Abstract

The uterine cervix is one of the key factors involved in ensuring a proper track of gestation and labor. At the end of the gestational period, the cervix undergoes extensive changes, which can be summarized as a transformation from a non-favorable cervix to one that is soft and prone to dilation. During a process called cervical ripening, fundamental remodeling of the cervical extracellular matrix (ECM) occurs. The cervical ripening process is a derivative of many interlocking and mutually driving biochemical and molecular pathways under the strict control of mediators such as inflammatory cytokines, nitric oxide, prostaglandins, and reactive oxygen species. A thorough understanding of all these pathways and learning about possible triggering factors will allow us to develop new, better treatment algorithms and therapeutic goals that could protect women from both dysfunctional childbirth and premature birth. This review aims to present the possible role of the NLRP3 inflammasome in the cervical ripening process, emphasizing possible mechanisms of action and regulatory factors.

Keywords: NLRP3 inflammasome; cervical ripening; inflammation; parturition.

Figure 1

Scheme showing the overall course of biochemical and molecular pathways occurring during cervical ripening; ROS—reactive oxygen species; IL-1—interleukin-1; NF-kB—nuclear factor kappa-B; IL-18—interleukin-18; p38MAPK—p38 mitogen-activated protein kinase; PGs—prostaglandins; NO—nitric oxide; MMPs—metalloproteinases.

Figure 2

Diagram showing possible role of NLPR3 inflammasome in cervical ripening; NF-kB—nuclear factor kappa-B; ROS—reactive oxygen species; IL-1—interleukin-1; IL-18—interleukin-18; p38MAPK—p38 mitogen-activated protein kinase; PGs—prostaglandins; NO—nitric oxide; MMPs—metalloproteinases; COX-2—cyclooxygenase-2; TNF-α—tumor necrosis factor-α; HAS—hyaluronan synthase; HA—hyaluronan.