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.