Testosterone‐Induced Pyroptotic Death of Ovarian Granulosa Cells in PCOS Might Involve Both GSDMD and GSDME, the Latter Possibly Enabling a Crosstalk Between Apoptosis and Pyroptosis

Pyroptosis is a pro-inflammatory regulated necrosis initiated by the member proteins of the gasdermin family (GSDMA, GSDMB, GSDMC, GSDMD, GSDME, and GSDMF) upon certain stimuli.Gasdermins consist of a cytotoxic N-terminal (NT) domain, a flexible linker region, and a C-terminal (CT) regulatory domain that binds to and inhibits the N-terminus (auto-inhibition), with the exception of GSDMF, also known as PJVK [ 1 ].Canonically, proteolytic cleavage within this linker region frees the NT domain of gasdermins, enabling it to target cellular membranes, such as nuclear, mitochondrial, and plasma membranes.Gasdermin-mediated formation of large transmembrane pores in the plasma membrane enables the release of certain proinflammatory cytokines such as IL-18, promoting inflammation [ 1,2 ].