Mitochondrial role in adaptive response to stress conditions in preeclampsia
Open accessAbstract
Preeclampsia (PE) is a pregnancy-specific syndrome, characterized in general by hypertension with proteinuria or other systemic disturbances. PE is the major cause of maternal and fetal morbidity and mortality worldwide. However, the etiology of PE still remains unclear. Our study involved 38 patients: 14 with uncomplicated pregnancy; 13 with early-onset PE (eoPE); and 11 with late-onset PE (loPE). We characterized the immunophenotype of cells isolated from the placenta and all biopsy samples were stained positive for Cytokeratin 7, SOX2, Nestin, Vimentin, and CD44. We obtained a significant increase in OPA1 mRNA and protein expression in the eoPE placentas. Moreover, TFAM expression was down-regulated in comparison to the control (p < 0.01). Mitochondrial DNA copy number in eoPE placentas was significantly higher than in samples from normal pregnancies. We observed an increase of maximum coupled state 3 respiration rate in mitochondria isolated from the placenta in the presence of complex I substrates in the eoPE group and an increase of P/O ratio, citrate synthase activity and decrease of Ca(2+)-induced depolarization rate in both PE groups. Our results suggest an essential role of mitochondrial activity changes in an adaptive response to the development of PE.
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Women with early-onset preeclampsia had a five-fold decrease in the mitochondrial transcription factor (TFAM)-A.
“2) a five-fold decrease in the mitochondrial transcription factor (TFAM)-A;”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [208]
Both early and late preeclampsia are associated with an elevated P/O ratio.
“while both early and late preeclampsia are associated with an elevated P/O ratio(208).”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [208]
Early-onset preeclampsia is associated with mitochondrial activation, up-regulation of OPA-1, active DNA replication (resulting from a high respiration rate), and TFAM down-regulation.
“Thus, early-onset preeclampsia is associated with mitochondrial activation, up-regulation of OPA-1, active DNA replication (resulting from a high respiration rate), and TFAM down-regulation, while both early and late preeclampsia are associated with an elevated P/O ratio(208).”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [208]
Women with early-onset preeclampsia had increased mitochondrial respiration in the presence of Complex I substrates.
“and 4) increased mitochondrial respiration in the presence of Complex I substrates(208).”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [208]
Women with early-onset preeclampsia had a 1.5-fold increase of the relative placental mitochondrial DNA copy number.
“3) a 1.5-fold increase of the relative placental mitochondrial DNA copy number;”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [208]
Women with early-onset preeclampsia had a two-fold increase in the mRNA expression of OPA-1 and a three-fold increase in OPA-1 protein expression (cleaved and uncleaved forms).
“Women with early-onset preeclampsia had 1) a two-fold increase in the mRNA expression of OPA (optic atrophy)-1 and a three-fold increase in OPA-1 protein expression (cleaved and uncleaved forms) in patients with early-onset preeclampsia.”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [208]
An increase in the P/O ratio was observed in both early and late preeclampsia.
“An increase in the P/O ratio (a measure for how much ATP is synthesized per 2 electrons transferred to oxygen) was observed in both early and late preeclampsia.”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [208]
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- Authors
- Vishnyakova, P. A., Volodina, M. A., Tarasova, N. V., Marey, M. V., Tsvirkun, D. V., Vavina, O. V., Khodzhaeva, Z. S., Kan, N. E., Menon, R., Vysokikh, M. Y., & Sukhikh, G. T.
- Affiliations
- Lomonosov Moscow State University (RU)
- National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I.Kulakov of the Ministry of Healthcare of the Russian Federation (RU)
- The University of Texas Medical Branch at Galveston (US)
- Corresponding author
- Vishnyakova, Polina A.
- ORCID
- Venue
- Scientific Reports
- Published
- 2016-08-30
- Volume
- 6
- Issue
- 1
- Pages
- 32410-32410
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5004102
- OpenAlex
- W2509286304
- Cited by
- 88
- References
- 51
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 5 · 2023: 7 · 2022: 11 · 2021: 11 · 2020: 11 · 2019: 14 · 2018: 10 · 2017: 6 · 2016: 1
- FWCI
- 13.35
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Russian Foundation for Basic Research
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- preeclampsia, mitochondrial dysfunction, placenta, early-onset preeclampsia, late-onset preeclampsia, OPA1, TFAM, mitochondrial DNA copy number, mitochondrial respiration, P/O ratio, citrate synthase, stress response
- MeSH terms
- Adult, DNA-Binding Proteins, Female, Gene Expression Regulation, Humans, Hypertension, Mitochondria, Placenta, Pre-Eclampsia, Pregnancy, RNA, Messenger, Stress, Physiological, Transcription Factors, Immunophenotyping, GTP Phosphohydrolases, Mitochondrial Proteins, Electron Transport Complex I
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