Induction of Hyperandrogenism and Insulin Resistance Differentially Modulates Ferroptosis in Uterine and Placental Tissues of Pregnant Rats

The study investigated the effects of hyperandrogenism and insulin resistance (HAIR) on ferroptosis in the uterine and placental tissues of pregnant rats, simulating conditions similar to polycystic ovary syndrome (PCOS) in humans. It found that HAIR led to increased fetal loss, with the uterus showing decreased levels of Gpx4 and glutathione (GSH), increased oxidative stress markers, and changes in ferroptosis-associated gene expression, indicating activation of ferroptosis. In contrast, the placenta showed only partial changes in ferroptosis markers. The study concluded that HAIR-induced ferroptosis in the uterus and placenta might contribute to fetal loss, with different molecular mechanisms involved in each tissue, and suggested that other cell death pathways, such as necroptosis and apoptosis, might also play roles in this process.