Figure 4.

The role of pyroptosis in the occurrence and development of pregnancy-related diseases (Created with BioRender.com). (A) MHF may cause high blood pressure in adult offspring. It also lead to the down-regulation of fetal renal peroxisomal markers PEX3 and 14, decreased antioxidant SOD2 and catalase, and elevated oxidative stress marker Ephx2 (61); (B) PA can activate NLRP3 inflammatory vesicles, resulting in significant caspase-1 activation and IL-1β secretion (62); (C) HMGB1 activates the NF-κB signaling pathway, NLRP-3 inflammatory vesicle assembly, caspase-1 protein activation, and release of inflammatory factors, ultimately inducing aseptic inflammation. This leads to the disruption of the maternal-fetal interface and the development of URSA (68); (D) ZIKV infection can activate RIG-I, which recognizes the viral genome and causes placental cell pyroptosis. This leads to the release of TNF-α, which activates caspase-8 and caspase-3, resulting in the cleavage of GSDME in placental cells (73); (E) miR-124-3p mimics increased the expression of NLRP3, caspase1 and IL-1β (107); (F) Nrf2 deficiency upregulates GSDMD expression, thereby exacerbating maternal hypoxia-induced pyroptosis in IUGR offspring (123). MHF, high-fat maternal; PEX, peroxisomes; SOD2, Superoxide Dismutase 2; HMGB1, high mobility group box-1; ZIKV, Zika virus; Nrf2, Nuclear factor erythroid-derived 2-related factor 2.