Circulating biomarkers of oxidative stress and extracellular nucleic acids as candidate markers of uterine scar integrity: Biological rationale and a research agenda
DOI:
https://doi.org/10.37800/RM.3.2026.837Keywords:
uterine scar dehiscence, oxidative stress, advanced oxidation protein products, cell-free DNA, fragmentomicsAbstract
Relevance: A scarred uterus is among the commonest conditions in obstetrics, and its failure during a trial of labor remains rare and hard to foresee. Prediction rests on ultrasound of the lower uterine segment and clinical history. Segment thickness discriminates rupture risk well, yet no circulating molecular marker is used in practice, and ultrasound reports the scar’s geometry, not the biology of one about to give way.
The study aimed to build a testable biological case for two families of blood-borne candidate markers of uterine scar integrity—oxidative stress and extracellular nucleic acids—and to set out a program for evaluating them.
Materials and Methods: Narrative, hypothesis-generating review. We searched PubMed, Scopus, and Web of Science for evidence over the past five years on uterine scar healing and dehiscence, oxidative-stress biomarkers in pregnancy, and cell-free nucleic acids as tissue-injury markers. No primary study has measured these markers as predictors of scar dehiscence, so candidates were drawn from adjacent, established literatures.
Results: Once Nrf2-governed antioxidant defense is overwhelmed, reactive oxygen species impair collagen synthesis and tip the matrix-metalloproteinase balance toward breakdown; advanced oxidation protein products, malondialdehyde, and reduced total antioxidant capacity are measurable in maternal blood and rise in pregnancy complications. Total cell-free DNA rises with tissue injury, while fragmentomic and methylation-based methods can infer a fragment’s tissue of origin, raising the possibility that a scar under strain in labor releases a localizable signal. We place these on a two-axis model anchored to ultrasound; labor perturbs both signals, and neither is scar-specific.
Conclusion: Oxidative-stress and extracellular-nucleic-acid markers are biologically plausible and measurable in maternal blood, but untested against this outcome; they are candidates, not validated predictors. The main obstacles are rupture’s rarity and confounding by labor. A staged program with falsifiable predictions is the next step.
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