NLRP3 inflammasome pathway, the hidden balance in pregnancy: A comprehensive review

The balance of the inflammatory response is indispensable during pregnancy. Inflammasomes are the cytosolic supramolecular protein complexes activated by pattern recognition receptors. These receptors recognize the pathogen and damage/danger-associated molecular patterns. NLRP3 inflammasome complex consists mainly of NLRP3 (leucine-rich repeat-containing and pyrin domain-containing protein 3), a cytosolic sensor molecule, ASC (apoptosis-associated speck-like protein containing a CARD) protein and a cysteine protease pro-caspase-1 as an effector molecule. This complex has a role in producing inflammatory cytokines, interleukin 1 beta and interleukin 18, and inflammasome-dependent programmed cell death pathway pyroptosis. In this review, we focused on and summarised the NLRP3 inflammasome and its roles in normal and pathological pregnancies. The NLRP3 inflammasome pathway influences endometrial receptivity and embryo invasion by inducing epithelial-mesenchymal transition. Abnormal inflammasome activation in the endometrium may adversely affect endometrial receptivity. In addition, NLRP3 inflammasome pathway overactivation may mediate the abnormal inflammatory response at the maternal-fetal interface and be associated with pregnancy complications, such as recurrent implantation failure, pregnancy loss, pre-term birth and pre-eclampsia. Therefore, targeting the NLRP3 inflammasome pathway could develop a new therapeutic approach to prevent the aforementioned pregnancy pathologies.