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.