5.3 POI
POI, characterized as early exhaustion of primordial follicles that may
cause low fertility, affects about 1% of women under the age of
40.74 This condition typically results from flaws in
the development of follicular atresia. Of note, previous researches have
confirmed the strong connection between ferroptosis and follicular
atresia and oocyte loss.10, 75 A latest study found
that BNC1 loss causes excessive follicular atresia and early follicular
activation by inducing oocyte ferroptosis via the NF2-YAP pathway, in
accordance with earlier findings that BNC1 mutation is related to
ovarian dysfunction through genome whole exon sequencing and transgenic
mouse animal models.76, 77 The levels of
ferroptosis-associated markers were aberrant in Bnc1 truncated mutant
mouse oocytes, and the corresponding phenotype was aggravated by the
ferroptosis agonist RLS3 and reversed by fer-1. This study also
discovered the downstream target gene Nf2 of BNC1 and the mechanism
governing the HiPO-YEP-TFRC/ACSL4 pathway, which controls oocyte
ferroptosis and is mediated by Nf2.
Ferroptosis and pregnancy diseases
Normally, during pregnancy, iron levels in pregnant women will increase
to meet the requirements of maternal and infant hematopoiesis. In
addition, hepcidin (hepc), an important regulator of iron homeostasis,
has been identified that the expression level decreased, and thus both
dietary iron absorption and stored iron release rise during normal
pregnancy. These findings imply the capacity to react to ambient iron
exposure may be diminished in healthy pregnant women, which may easily
lead to clinical diseases due to excessive iron.78Recent years, several pregnancy diseases have been uncovered their
pathogenesis is linked with ferroptosis.79, 80
6.1 PE
PE is a common disease of pregnancy, about 3–10% of all pregnant women
suffer from preeclampsia worldwide, and together with
eclampsia,81 It is a significant contributor to poor
pregnancy outcomes and maternal mortality; over 50,000 mothers die from
them each year across the globe.82 The exact reason
for preeclampsia is unclear, a key pathophysiologic feature though is
the development of an abnormal placenta which may be linked with
ferroptosis.