Placental oxidative stress: from miscarriage to preeclampsia
Abstract
Objective To review the role of oxidative stress in two common placental-related disorders of pregnancy, miscarriage and preeclampsia.Methods Review of published literature.Results Miscarriage and preeclampsia manifest at contrasting stages of pregnancy, yet both have their roots in deficient trophoblast invasion during early gestation. Early after implantation, endovascular trophoblast cells migrate down the lumens of spiral arteries, and are associated with their physiological conversion into flaccid conduits. Initially these cells occlude the arteries, limiting maternal blood flow into the placenta. The embryo therefore develops in a low oxygen environment, protecting differentiating cells from damaging free radicals. Once embryogenesis is complete, the maternal intervillous circulation becomes fully established, and intraplacental oxygen concentration rises threefold. Onset of the circulation is normally a progressive periphery-center phenomenon, and high levels of oxidative stress in the periphery may induce formation of the chorion laeve. If trophoblast invasion is severely impaired, plugging of the spiral arteries is incomplete, and onset of the maternal intervillous circulation is premature and widespread throughout the placenta. Syncytiotrophoblastic oxidative damage is extensive, and likely a major contributory factor to miscarriage. Between these two extremes will be found differing degrees of trophoblast invasion compatible with ongoing pregnancy but resulting in deficient conversion of the spiral arteries and an ischemia-reperfusion-type phenomenon. Placental perfusion will be impaired to a greater or lesser extent, generating commensurate placental oxidative stress that is a major contributory factor to preeclampsia.Conclusion Miscarriage, missed miscarriage, and early- and late-onset preeclampsia represent a spectrum of disorders secondary to deficient trophoblast invasion.
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Gui et al. suggested that metformin reduced the rate of gestational hypertension because of its effects on endothelial function and its decrease in the production of reactive oxygen species.
“Gui et al.(75) suggested that metformin reduced the rate of gestational hypertension because of its effects on endothelial function and its decrease in the production of reactive oxygen species, the two mechanisms implicated in the pathophysiology of preeclampsia(84–94).”
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 [90]
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Self-citationHastie, R., & Lappas, M. (2014) · Placenta · doi:10.1016/j.placenta.2014.06.368 · Cited by 107 · see citing works
Mechanisms regulating cytotrophoblast invasion in normal pregnancy and pre‐eclampsia
Lyall, F. (2006) · Australian and New Zealand Journal of Obstetrics and Gynaecology · doi:10.1111/j.1479-828x.2006.00589.x · Cited by 106 · see citing works
Chelbi, S. T., Wilson, M. L., Veillard, A.-C., Ingles, S. A., Zhang, J., Mondon, F., Gascoin-Lachambre, G., Doridot, L., Mignot, T.-M., Rebourcet, R., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds006 · Cited by 106 · see citing works
- Authors
- Burton, G. J., & Jauniaux, E.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Burton, Graham J.
- Venue
- Journal of the Society for Gynecologic Investigation
- Published
- 2004-09
- Volume
- 11
- Issue
- 6
- Pages
- 342-352
- ISSN
- 1071-5576 (ISSN-L)
- OpenAlex
- W1972766975
- Cited by
- 673
- References
- 109
- Citations by year
- 2026: 16 · 2025: 22 · 2024: 25 · 2023: 22 · 2022: 42 · 2021: 35 · 2020: 38 · 2019: 37 · 2018: 41 · 2017: 35 · 2016: 33 · 2015: 32 · 2014: 41 · 2013: 27 · 2012: 37
- FWCI
- 5.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the Society for Gynecologic Investigation (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (publishedVersion)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Health Sciences › Medicine › Psychiatry and Mental health › Neurological Complications and Syndromes
- Keywords
- placental oxidative stress, miscarriage, preeclampsia, trophoblast invasion, spiral artery remodeling, syncytiotrophoblast, chorion laeve, placental perfusion, missed abortion
- MeSH terms
- Abortion, Spontaneous, Adult, Female, Free Radicals, Humans, Placenta, Placenta Diseases, Pre-Eclampsia, Pregnancy, Reactive Oxygen Species, Oxidative Stress
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