Unraveling the role of sulfiredoxin-1 in early-onset preeclampsia: A key player in trophoblast ferroptosis

Abstract

Preeclampsia (PE) significantly contributes to obstetric complications and maternal mortality, yet its pathogenesis and mechanisms are not well understood. Sulfiredoxin-1 (SRXN1) is known for its antioxidant activity and its role in defending against oxidative stress; it is also linked to various cancers. However, the role of SRXN1 in PE remains unclear. Our study found a significant decrease in SRXN1 levels in the serum and placental tissues of patients with early-onset preeclampsia (EOPE). Similarly, a PE-like mouse model showed reduced SRXN1 expression. Our in vitro experiments showed that reducing SRXN1 impaired trophoblast viability, decreased invasion and migration, and led to cell death, primarily through ferroptosis. These results are consistent with analyses of placental tissues from EOPE patients. In summary, lower SRXN1 levels during pregnancy contribute to trophoblast ferroptosis, potentially affecting the development and progression of EOPE.