Spotlight on iron overload and ferroptosis: Research progress in female infertility

Iron is an essential trace element for organisms. However, iron overload, which is common in haematological disorders (e.g. haemochromatosis, myelodysplastic syndromes, aplastic anaemia, and thalassaemia, blood transfusion-dependent or not), can promote reactive oxygen species generation and induce ferroptosis, a novel form of programmed cell death characterised by excess iron and lipid peroxidation, thus causing cell and tissue damage. Infertility is a global health concern. Recent evidence has indicated the emerging role of iron overload and ferroptosis in female infertility by inducing hypogonadism, causing ovary dysfunction, impairing preimplantation embryos, attenuating endometrial receptivity, and crosstalk between subfertility-related disorders, such as polycystic ovary syndrome and endometriosis. In addition, gut microbiota and their metabolites are involved in iron metabolism, ferroptosis, and female infertility. In this review, we systematically elaborate on the current research progress in female infertility with a novel focus on iron overload and ferroptosis and summarise promising therapies targeting iron overload and ferroptosis to recover fertility in women. In summary, our study provides new insights into female infertility and offers literature references for the clinical management of female infertility associated with iron overload and ferroptosis, which may be beneficial for females with haematopoietic disorders suffering from both iron overload and infertility.