NRF1 and NRF2 Expression in Preeclamptic Placentas: A Comparative Observational Study.

Area of Science:

• Obstetrics and Gynecology
• Molecular Biology
• Biochemistry

Background:

• Preeclampsia (PE) is a pregnancy disorder linked to oxidative stress and mitochondrial dysfunction.
• Nuclear factor erythroid 2-related factor 1 (NRF1) and NRF2 are key regulators of mitochondrial function and antioxidant defenses.
• Investigating NRF1 and NRF2 placental expression is crucial for understanding PE pathophysiology.

Purpose of the Study:

• To examine the expression patterns of NRF1 and NRF2 in placentas from women with preeclampsia (PE) and severe preeclampsia (sPE).
• To explore the potential clinical relevance of NRF1 and NRF2 as biomarkers and therapeutic targets in PE.

Main Methods:

• Immunohistochemistry and bioinformatic analyses were performed on placental tissues from 40 healthy controls, 40 PE patients, and 40 sPE patients.
• Protein-protein interaction networks were constructed using STRING and Cytoscape.
• Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted using ShinyGO.

Main Results:

• NRF1 expression was significantly reduced in PE and sPE placentas, particularly in syncytial knots and fibrinoid areas.
• NRF2 expression was significantly elevated in PE and sPE placentas, with strong positivity in syncytiotrophoblasts, stromal cells, and vascular structures.
• Pathway analysis linked decreased NRF1 to glutathione metabolism and HIF-1 signaling, while increased NRF2 was associated with inflammatory and immune responses.

Conclusions:

• Differential placental expression of NRF1 and NRF2 in PE reflects complex responses to oxidative stress and inflammation.
• NRF1 and NRF2 show potential as clinical biomarkers for assessing PE severity.
• These transcription factors represent potential targets for future therapeutic interventions in preeclampsia.