5.2 PCOS
About 15%–21% of women of reproductive age have PCOS, which is the
most frequent cause of anovulatory infertility and is characterized by
hyperandrogenism, insulin resistance, and irregular ovulation or
anovulation.65 Previous research discovered that the
primary factor behind the onset and progression of PCOS is aberrant
ovarian folliculogenesis.66 There are growing evidence
showing that ferroptosis may be associated with it. Therefore, it is
meaningful for us to understanding the mechanism of ferroptosis in PCOS
and discovery novel treatment for POCS-related infertility.
Several studies have identified that ferroptosis may have a key role in
the pathogenesis of PCOS. MiRNA and circ RNA can regulate the progress
of PCOS via ferroptosis. Circ RHBG has been shown to compete with
SLC7A11 for the ability to bind to miR-515-5p, upregulate the expression
of SLC7A11, and ultimately prevent GC ferroptosis.67However, Silencing MiR-93-5p guards against GCs dysfunction through
controlling the NF-B signaling pathway and encouraging GCs apoptosis and
ferroptosis.68
Moreover, the unique microenvironment in PCOS patients vivo causes
ferroptosis in gravid uterine and the placenta. The results of one study
showed that co-exposure to 5 dihydrotestosterone and insulin resulted in
decreased levels of glutathione and GPX4, altered expression of genes
related to ferroptosis such as ACSL4, SLC7A11, increased levels of the
oxidative stress marker malondialdehyde (MDA) and iron deposition,
increased levels of the ERK/p38/JNK pathway and mitochondrial
morphology.69 But the specific relationship between
ferroptosis and PCOS has not been illustrated. A previous study showed
that gravid uterine and placental ferroptosis is modulated by
hyperandrogenism and insulin resistance in PCOS.69Proteomic analysis of CD4+ T cells in infertile patients with PCOS
showed that three key proteins, which namely
phosphatidylethanolaminebinding protein 1, proteasome activator complex
subunit 1 and triosephosphate isomerase 1 are overexpressed are involved
in the ferroptosis pathway.70 We hypothesize that
ferroptosis may have an impact on PCOS-related infertility. Of note, it
was revealed by differential gene expression analysis that the
interaction of autophagy, apoptosis, and ferroptosis contributed to the
development of porcine ovarian atresia.10
In addition, these ferroptosis inhibitors,
Ferrostatin‑1,71 N-acetylcysteine,72Cryptotanshinone,73 have shown that they can relieve
symptoms in PCOS patients. Ferroptosis is generally considered to be
intimately associated with the pathogenic alterations of PCOS, while the
precise mechanism is still currently unclear. Overall, the present
studies have explored the role of ferroptosis in the pathological
process of PCOS, targeting the inhibition of ferroptosis may be an
effective treatment for PCOS.