Upregulation of TXNIP contributes to granulosa cell dysfunction in polycystic ovary syndrome via activation of the NLRP3 inflammasome

Polycystic ovary syndrome (PCOS) is a complex endocrine disease. Thioredoxin-interacting protein (TXNIP) promotes oxidative stress and triggers inflammation. Herein, we investigated the role and potential mechanism of TXNIP in PCOS. In a mouse model of dehydroepiandrosterone (DHEA)-induced PCOS, we found that TXNIP was upregulated in the ovaries, especially in granulosa cells (GCs). TXNIP was also upregulated in testosterone (T)-treated GCs in vitro. Knockdown of TXNIP by lentivirus-constructed shRNA attenuated T-induced GC injury and oxidative stress, as well as inflammation and the NLRP3 inflammasome. The mechanism by which TXNIP promotes inflammation may involve TXNIP dissociation from the TXNIP-TRX complex and binding to NLRP3 to form the inflammasome. Additionally, we verified that knockdown of TXNIP ameliorated ovarian injury and inflammation in mice with DHEA-induced PCOS in vivo. Collectively, we demonstrated that TXNIP is involved in GC inflammation by promoting NLRP3 inflammasome activation in PCOS.

Automated summary

In this study, we investigated the role and mechanism of TXNIP in PCOS. TXNIP was found to be upregulated in the ovaries of PCOS mice and testosterone-treated granulosa cells. Knockdown of TXNIP attenuated GC injury, oxidative stress, inflammation, and NLRP3 inflammasome activation. Furthermore, knockdown of TXNIP ameliorated ovarian injury and inflammation in mice with DHEA-induced PCOS. These findings suggest that TXNIP is involved in GC inflammation by promoting NLRP3 inflammasome activation in PCOS.