Mitochondrial ROS Accumulation Contributes to Maternal Hypertension and Impaired Remodeling of Spiral Artery but Not IUGR in a Rat PE Model Caused by Maternal Glucocorticoid Exposure
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Measurement of Blood Pressure
2.3. Uteroplacental Blood Perfusion Measurement
2.4. Measurement of Urinary Protein/Creatinine Concentration
2.5. Pathological Assessment of the Kidney
2.6. Pathological Immunostaining of Placental Tissue
2.7. Electron Microscopy
2.8. Enzyme-Linked Immunosorbent Assay (ELISA)
2.9. Transcriptome Sequencing Analysis
2.10. Targeted Metabolomics
2.11. Cell Culture and In Vitro Trophoblast Migration and Invasion Assessment
2.12. Assay of Mitochondrial Oxygen Consumption
2.13. Mitochondrial Isolation and Function Determination
2.14. Total RNA Extraction and Quantitative Real-Time PCR (Q-PCR)
2.15. Mitochondrial DNA Copy Number Detection
2.16. Western Blotting Analysis
2.17. Statistical Analysis
3. Results
3.1. DEX Induces PE-like Features and Results in Changes in a Large Spectrum of the Transcriptome in Placentas of Pregnant Rats
3.2. Placental Mitochondrial Function and Morphology Are Impaired, and Mitochondrial ROS Production Is Significantly Increased in the DEX-Induced PE Model
3.3. Scavenging mtROS Significantly Reverses Maternal Hypertension and Improves Renal Damage but Not IUGR and Elevated Circulatory sFlt-1 and sEng Levels in DEX-Induced PE Rats
3.4. Scavenging mtROS Significantly Partly Improves the Expression of the Factors in OXPHOS, Mitochondrial Function and Morphology in DEX Rats
3.5. MtROS Accumulation Contributes to Impaired SA Remodeling, Uteroplacental Blood Flow and Placental Hypoxia but Not Fetal Blood Flow in DEX-Induced PE Rats
3.6. MitoTEMPO Treatment Reverses Some Pathways Including OXPHOS and Glutathione Pathways and Improves mtDNA Copy in DEX-Induced PE Rats
3.7. Impaired Glycolysis and Pentose Phosphate Pathway (PPP) Induced by DEX Might Not Be Associated with Excess ROS
3.8. Excess ROS May Not Contribute to DEX-Induced Alternation of Transcriptional Levels of Placental Cytokines, Prostaglandin Biosynthetic Process and Growth Factors and Increased Circulatory Levels of Proinflammatory Cytokines and PGE2 in DEX-Induced PE Rats
3.9. DEX Impairment of Human EVTs Function Is Associated with Excess ROS Due to Mitochondrial Dysfunction
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Long, J.; Huang, Y.; Wang, G.; Tang, Z.; Shan, Y.; Shen, S.; Ni, X. Mitochondrial ROS Accumulation Contributes to Maternal Hypertension and Impaired Remodeling of Spiral Artery but Not IUGR in a Rat PE Model Caused by Maternal Glucocorticoid Exposure. Antioxidants 2023, 12, 987. https://doi.org/10.3390/antiox12050987
Long J, Huang Y, Wang G, Tang Z, Shan Y, Shen S, Ni X. Mitochondrial ROS Accumulation Contributes to Maternal Hypertension and Impaired Remodeling of Spiral Artery but Not IUGR in a Rat PE Model Caused by Maternal Glucocorticoid Exposure. Antioxidants. 2023; 12(5):987. https://doi.org/10.3390/antiox12050987
Chicago/Turabian StyleLong, Jing, Yan Huang, Gang Wang, Zhengshan Tang, Yali Shan, Shiping Shen, and Xin Ni. 2023. "Mitochondrial ROS Accumulation Contributes to Maternal Hypertension and Impaired Remodeling of Spiral Artery but Not IUGR in a Rat PE Model Caused by Maternal Glucocorticoid Exposure" Antioxidants 12, no. 5: 987. https://doi.org/10.3390/antiox12050987
APA StyleLong, J., Huang, Y., Wang, G., Tang, Z., Shan, Y., Shen, S., & Ni, X. (2023). Mitochondrial ROS Accumulation Contributes to Maternal Hypertension and Impaired Remodeling of Spiral Artery but Not IUGR in a Rat PE Model Caused by Maternal Glucocorticoid Exposure. Antioxidants, 12(5), 987. https://doi.org/10.3390/antiox12050987