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<p>Polycystic ovary syndrome (PCOS) is a complex endocrine disorder characterized by increased levels of androgens (hyperandrogenism), irregular menstruation, ovulatory dysfunction, polycystic ovaries and insulin resistance, affecting around 5–20% of women of reproductive age. Bile acids are amphipathic steroid molecules regulating various physiological processes. The levels of different bile acids in the various organs and&#xa0;in the serum, stool and follicular fluid samples of patients with PCOS have been shown to be altered (either increased or decreased) in multiple studies. Pyroptosis is a programmed (regulated) cell death mechanism characterized by the excessive release of pro-inflammatory cytokines (such as IL-18), leading to inflammation. Pyroptotic death of granulosa cells in the ovaries are involved in the pathogenesis of PCOS. Bile acids and bile acid metabolites have been shown to be involved in the activation or inhibition of pyroptotic cell death in different contexts. Here, based on these previous observations, we hypothesize that bile acid-mediated regulation of pyroptosis might be involved in the pathogenesis of&#xa0;PCOS. This might suggest that certain effects of bile acids in the context of PCOS might be via their influence on the&#xa0;pyroptotic cell death of certain&#xa0;ovarian&#xa0; cell types which are important for ovarian biology, such as granulosa cells. In PCOS, changes in the levels of multiple bile acids might be responsible for the observed changes in pyroptotic events&#xa0;in the ovaries. Since it is now known that bile acids might lead to increases or decreases in the levels of pyroptosis in particular contexts, bile acid-mediated changes in pyroptotic cell death might be a mechanism of high clinical importance in PCOS, linking liver and ovarian health.</p>

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Bile acid-mediated regulation of pyroptosis in PCOS: a hypothesis for hepato-ovarian axis

  • 期刊论文

  • 发表日期：

    2026年4月24日

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  • Sukran Yagmur Avcioglu,
  • Caglar Berkel

摘要

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder characterized by increased levels of androgens (hyperandrogenism), irregular menstruation, ovulatory dysfunction, polycystic ovaries and insulin resistance, affecting around 5–20% of women of reproductive age. Bile acids are amphipathic steroid molecules regulating various physiological processes. The levels of different bile acids in the various organs and in the serum, stool and follicular fluid samples of patients with PCOS have been shown to be altered (either increased or decreased) in multiple studies. Pyroptosis is a programmed (regulated) cell death mechanism characterized by the excessive release of pro-inflammatory cytokines (such as IL-18), leading to inflammation. Pyroptotic death of granulosa cells in the ovaries are involved in the pathogenesis of PCOS. Bile acids and bile acid metabolites have been shown to be involved in the activation or inhibition of pyroptotic cell death in different contexts. Here, based on these previous observations, we hypothesize that bile acid-mediated regulation of pyroptosis might be involved in the pathogenesis of PCOS. This might suggest that certain effects of bile acids in the context of PCOS might be via their influence on the pyroptotic cell death of certain ovarian  cell types which are important for ovarian biology, such as granulosa cells. In PCOS, changes in the levels of multiple bile acids might be responsible for the observed changes in pyroptotic events in the ovaries. Since it is now known that bile acids might lead to increases or decreases in the levels of pyroptosis in particular contexts, bile acid-mediated changes in pyroptotic cell death might be a mechanism of high clinical importance in PCOS, linking liver and ovarian health.