Preeclampsia is Associated with Altered Expression of Ferroptosis Biomarkers in Placental but not Maternal Vasculature
Name
43032_2025_1935_ReferencePDF.pdf
Size
698.89 KB
Format
Adobe PDF
Checksum (MD5)
f795a7c62658d44af70a0c65eda74fe9
Author(s)
Ng, Shu-Wing
Ng, Allen C.
Ng, Michelle C.
Ng, Shu-Kay
Arcuri, Felice
Genega, Elizabeth M.
Watkins, Jaclyn C.
Roberts, Drucilla J.
House, Michael D.
O’Tierney-Ginn, Perrie F.
Date Issued
August 6, 2025
Journal
Reproductive Sciences
Publisher
Springer International Publishing
Citation
Ng, SW., Ng, A.C., Ng, M.C. et al. Preeclampsia is Associated with Altered Expression of Ferroptosis Biomarkers in Placental but not Maternal Vasculature. Reprod. Sci. 32, 3074–3085 (2025).
Version
Author's final manuscript
Abstract
Ferroptosis, an iron-dependent mechanism of programmed cell death, has been implicated in the pathogenesis of preeclampsia (PE). Here, we investigate the expression of key ferroptosis biomarkers in placental and decidua basalis tissues. Immunohistochemical (IHC) staining showed high expression of the ferroptosis suppressor, ferroptosis-suppressor protein 1 (FSP1), and the end product malondialdehyde (MDA), in healthy CD31-positive placental endothelium. The staining of all three markers was significantly reduced in PE placentas (P = 0.028). In vitro studies showed that an immortalized endometrial endothelial cell line, and its fetal counterpart, human umbilical vein endothelial cells, are intrinsically highly resistant to erastin-induced ferroptotic cell death compared with trophoblast, endometrial epithelial, and stromal fibroblast cell types. FSP1 was specifically expressed in the endometrial endothelial cells. Both FSP1 and another ferroptosis suppressor protein, GPX4, were degraded when the cells underwent ferroptotic cell death. Interestingly, staining of these same markers in maternal decidua basalis tissues did not show endothelium-specific staining, and no significant difference in staining was noted between healthy and PE tissues. Since previous studies have shown that endometrial cells can activate ferroptosis to produce pro-angiogenic cytokines, we posit that healthy placental endothelial cells activate ferroptosis, as evidenced by high MDA, to promote vasculature development without undergoing cell death, whereas PE placentas show reduced ferroptosis and vasculature underdevelopment. In contrast, both healthy and PE decidua basalis tissues were considered to be in a resting stage with regard to ferroptosis. Further studies are warranted to investigate how ferroptosis is regulated in both healthy and PE pregnancies.
MIT Department
Massachusetts Institute of Technology. Center for Gynepathology Research
Terms of Use
Creative Commons Attribution-Noncommercial-ShareAlike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1007/s43032-025-01935-2
