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Updated: Jun 9, 2025
Author Spotlight: Modeling an Aspect of Preeclampsia in Female Mice Using Hypoxic Human Placenta-Derived Small Extracellular Vesicles
Published on: January 26, 2024
Senescent Syncytiotrophoblast Secretion During Early Onset Preeclampsia
Olivia Nonn1,2,3,4,5, Olivia Debnath6, Daniela S Valdes1,2,3,4
1Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany (O.N., D.S.V., J.U., H.B., A.F., N.H., K.K., S.K., D.N.M., R.D., F.H.).
Insights
Preeclampsia is predicted by placental senescence markers, like PAI-1 and activin A, appearing in maternal blood weeks before symptoms. This discovery offers potential for early diagnosis of preeclampsia.
Area of Science:
- Reproductive biology
- Genomics
- Pathology
Background:
- Preeclampsia is a serious pregnancy complication causing preterm birth and long-term cardiovascular risks.
- Current early predictive tests and therapies for preeclampsia are limited.
- Understanding preeclampsia pathogenesis is crucial for maternal and fetal health.
Purpose of the Study:
- To identify novel biomarkers and signaling pathways for early-onset preeclampsia.
- To investigate the role of placental changes in preeclampsia development.
Main Methods:
- Single-nucleus RNA sequencing and spatial transcriptomics were used to profile maternal-fetal interface units.
- Placental tissues from early-onset preeclampsia and healthy controls were analyzed.
- Senescence markers and secreted factors were quantified in maternal blood.
Main Results:
- Transcriptomic analysis revealed dysregulated senescence in placental syncytiotrophoblast.
- Elevated senescence markers were confirmed in clinical preeclampsia cohorts.
- Specific senescence-associated secretory phenotype factors, PAI-1 and activin A, were elevated in first-trimester maternal blood, predicting preeclampsia.
Conclusions:
- Increased syncytiotrophoblast senescence precedes clinical preeclampsia manifestation by weeks.
- Premature placental senescence and associated secretory phenotype release contribute to preeclampsia.
- Senescence markers show promise as early diagnostic tools for preeclampsia.
Background:
Preeclampsia is a severe hypertensive disorder in pregnancy that causes preterm delivery, maternal and fetal morbidity, mortality, and life-long sequelae. Understanding the pathogenesis of preeclampsia is a critical first step toward protecting mother and child from this syndrome and increased risk of cardiovascular disease later in life. However, effective early predictive tests and therapies for preeclampsia are scarce.
Methods:
To identify novel markers and signaling pathways for early onset preeclampsia, we profiled human maternal-fetal interface units (fetal villi and maternal decidua) from early onset preeclampsia and healthy controls using single-nucleus RNA sequencing combined with spatial transcriptomics. The placental syncytiotrophoblast is in direct contact with maternal blood and forms the barrier between fetal and maternal circulation.
Results:
We identified different transcriptomic states of the endocrine syncytiotrophoblast nuclei with patterns of dysregulation associated with a senescence-associated secretory phenotype and a spatial dysregulation of senescence in the placental trophoblast layer. Elevated senescence markers were validated in placental tissues of clinical multicenter cohorts. Importantly, several secreted senescence-associated secretory phenotype factors were elevated in maternal blood already in the first trimester. We verified the secreted senescence markers, PAI-1 (plasminogen activator inhibitor 1) and activin A, as identified in our single-nucleus RNA sequencing model as predictive markers before clinical preeclampsia diagnosis.
Conclusions:
This indicates that increased syncytiotrophoblast senescence appears weeks before clinical manifestation of early onset preeclampsia, suggesting that the dysregulated preeclamptic placenta starts with higher cell maturation resulting in premature and increased senescence-associated secretory phenotype release. These senescence-associated secretory phenotype markers may serve as an additional early diagnostic tool for this syndrome.
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