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.