Authors
Anya L Arthurs, Rudrarup Bhattacharjee, Melanie D Smith, Dulce L Medina Garcia, Ellen Menkhorst, German Mora, Jessica M Williamson, Lynda K Harris, Jose M Polo, David A MacIntyre, Claire T Roberts
Published in
Proceedings of the National Academy of Sciences of the United States of America. Volume 123. Issue 41. Pages e2614827123. Oct 13, 2026. Epub Oct 06, 2026.
Abstract
Late-onset preeclampsia (LOPE) is a major pregnancy complication characterized by hypertension and placental dysfunction, resolving only upon delivery. Here, we show that LOPE placentae undergo accelerated molecular aging, marked by telomere attrition, DNA damage, and trophoblast senescence. Using primary placental tissue and trophoblast organoids, we demonstrate oxidative stress as a driver of telomere shortening and angiogenic imbalance. Inflammation did not alter placental aging trajectories. Antioxidant treatment (superoxide dismutase) preserved telomere length, reduced DNA damage, and restored angiogenic balance, highlighting oxidative stress as a modifiable determinant of placental aging. We identify reduced expression of telomeric repeat-containing RNAs (TERRAs) as a molecular hallmark of LOPE, and show that antisense oligonucleotide-mediated TERRA depletion exacerbates telomere erosion and senescence. Together, these findings delineate oxidative stress and TERRA loss as mechanisms driving placental decline, establish trophoblast organoids as a tractable model of placental aging, and reveal potential therapeutic avenues for mitigating preeclampsia-associated placental dysfunction.
PMID:
42837445
Bibliographic data and abstract were imported from PubMed on 07 Oct 2026.
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