Iron Metabolism and Ferroptosis in Reproductive Health

Iron is indispensable for DNA synthesis, cell proliferation and hormone biosynthesis within reproductive tissues. Systemic iron homeostasis is orchestrated by intestinal absorption, hepatic storage and the iron‐regulatory hormone hepcidin, which controls ferroportin‐mediated iron export. Within the ovary and endometrium, tightly regulated iron levels ensure proper oocyte maturation, follicle development and endometrial receptivity. However, excessive labile iron catalyses lipid peroxidation and reactive oxygen species formation, triggering ferroptosis, a distinct form of regulated cell death. Emerging evidence implicates ferroptosis in the pathogenesis of reproductive disorders such as endometriosis, recurrent pregnancy loss and oocyte dysmaturity. Imbalances in iron uptake, storage and export can create a pro‐ferroptotic environment in granulosa cells, oocytes and decidual stromal cells, impairing fertility and pregnancy maintenance. Understanding the interplay between systemic iron regulation and local ferroptotic pathways offers insight into novel diagnostic markers and therapeutic strategies–from iron chelators and antioxidants to targeted modulation of ferroptosis regulators–with global implications for reproductive health and assisted conception outcomes.

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Iron Metabolism and Ferroptosis in Reproductive Health publication trend

The graph below shows the total number of articles in iron metabolism and ferroptosis in reproductive health across all publications each year (not limited to Nature Index journals).

Technical terms

Ferroptosis: Iron‐dependent regulated cell death characterised by lethal lipid peroxidation.

Hepcidin: Liver‐derived peptide hormone that inhibits iron export by degrading ferroportin.

Granulosa cells: Ovarian somatic cells that surround and nourish developing oocytes.

Decidual stromal cells: Maternal uterine cells transformed during pregnancy to support embryo implantation.

Lipid peroxidation: Oxidative degradation of lipids leading to membrane damage.

Follicular fluid: Nutrient‐rich medium in ovarian follicles that bathes oocytes and granulosa cells.

References

1. Double-edged roles of ferroptosis in endometriosis and endometriosis-related infertility. Cell Death Discovery (2023).
2. Decidual Stromal Cell Ferroptosis Associated with Abnormal Iron Metabolism Is Implicated in the Pathogenesis of Recurrent Pregnancy Loss. International Journal of Molecular Sciences (2023).
3. Iron-overloaded follicular fluid increases the risk of endometriosis-related infertility by triggering granulosa cell ferroptosis and oocyte dysmaturity. Cell Death & Disease (2022).