Pyroptosis in Ovarian Aging, and Its Influence on Female Reproductive Health in Aged Ovaries

Pyroptosis is a lytic cell death mechanism mediated by the gasdermin family of proteins, resulting in the release of certain pro-inflammatory molecules to the extracellular space. Ovaries serve as the source of oocytes and main producer of steroid sex hormones, making them essential with respect to the maintenance of fertility and endocrine homeostasis during reproductive lifespan in females. Ovaries exhibit early-onset aging-associated dysfunction, compared to most other tissues, with dramatic functional declines after only 30 years of age in women. In this review, I covered studies reporting the age-dependent changes in pyroptotic cell death in ovaries, and the effects of increased pyroptotic events in aged ovaries on the female reproductive health. Increased pyroptosis of diverse cell types in the ovarian microenvironment might adversely influence ovarian function and composition in the course of ovarian aging, mostly by its effects on inflammation and cellular senescence. Novel strategies targeting pyroptotic cell death in aging ovaries might alleviate certain adverse outcomes in terms of fertility or female reproductive health in general. Considering that many molecules which are known to inhibit pyroptosis are currently available, a better molecular understanding and evaluation of these pyroptosis inhibitors in the clinic for the mitigation of aging-associated declines in ovarian function and female fertility is needed.