Figure Legends
Figure 1. The brief activation mechanism of ferroptosis.
Excessive ROS, free iron, and lipid peroxidation all contribute to ferroptosis. Iron overload can result from increasing TfR1 or reducing ferritin expression (FTL and FTH1). In cells, the Fenton reaction results in a significant amount of ROS. PUFAs produce PUFA-PE and ROS under the influence of ASCL4 and LPAT3, ultimately cause ferroptosis. GPX4, a vital antioxidant enzyme in the body, has the ability to successfully anti-peroxide. Cys2, which is necessary for the production of GSH and is delivered by System Xc-, is essential for the operation of GPX 4.
Figure 2. The potential mechanism of ferroptosis in reproductive diseases.
In EMs,EECs are resistant to ferroptosis which allows them proliferation, migration and form ectopic tissue eventually, but ferroptosis can also promote the progress of EMs such as angiogenesis in surrounding tissues and leading to infertility, etc. In PCOS, Ferroptosis related proteins are highly expressed in infertile PCOS patients, and ferroptosis inhibitors can reduce the symptoms of polycystic ovary. In POI, Ferroptosis leads to premature apoptosis of ovarian cells, thus reducing ovarian reserve. In PE, iron overload, excessive ROS in vivo and other ferroptosis inducers lead trophoblast cells ferroptosis, and then lead placental injury. In GDM, higher BMI have a higher risk of β Cells ferroptosis, causing further increase of blood sugar. At the same time, high fat induced ferroptosis of trophoblasts, resulting in placental damage. In OC, ferroptosis inducers like erastin are thought as an effective drug to kill tumor cells and treat drug resistance.
Figure 3. The mechanism of ferroptosis-resistance in EMs.
Green represents the molecules that change in ectopic endometrium: the genes inducing ferroptosis ACSL4, LPCAT3 are downregulated. Moreover, ferritin and lnc RNA ADAMTS9-AS are upregulated, preventing ferroptosis. Blue represents the molecules that change in eutopic endometrium: the genes inducing ferroptosis including STA1, ALOX15, NCOA4, VDAC2 are downregulated in eutopic endometrium. FBLN1 which can increase ESC viability and migration by prohibiting ferroptosis are upregulated.