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Updated: Mar 1, 2026
Author Spotlight: Modeling an Aspect of Preeclampsia in Female Mice Using Hypoxic Human Placenta-Derived Small Extracellular Vesicles
Published on: January 26, 2024
Impaired functional capacity of fetal endothelial cells in preeclampsia
Lars Brodowski1, Jennifer Burlakov1, Sarah Hass1
1Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany.
Insights
Preeclampsia impairs fetal endothelial cell function, increasing cardiovascular risk. Vitamin D3 did not reverse these negative effects in this study, contrary to prior research.
Area of Science:
- Obstetrics and Gynecology
- Cardiovascular Research
- Cell Biology
Background:
- Preeclampsia is a significant cause of maternal and fetal mortality.
- Preeclampsia history increases long-term cardiovascular risk for mother and offspring.
- Fetal endothelial cell dysfunction may contribute to long-term cardiovascular risks associated with preeclampsia.
Purpose of the Study:
- To investigate functional impairments in fetal endothelial cells from preeclampsia pregnancies.
- To determine if 1,25(OH)2 vitamin D3 can reverse preeclampsia-associated endothelial cell dysfunction.
- To explore the impact of placental factors on fetal endothelial cell function.
Main Methods:
- Isolated human umbilical vein endothelial cells (HUVEC) from preeclamptic and control pregnancies.
- Utilized placental villous explant conditioned media (CM) from varying oxygen levels (hypoxia).
- Assessed HUVEC migration, proliferation, and tubule formation in response to CM and 1,25(OH)2 vitamin D3.
Main Results:
- HUVEC from preeclamptic pregnancies exhibited reduced migration and tubule formation.
- Hypoxic placental CM significantly impaired HUVEC migration.
- 1,25(OH)2 vitamin D3 did not improve HUVEC function in either group and did not affect VEGF expression.
Conclusions:
- Dysfunctional placental pathways in preeclampsia negatively impact fetal endothelial cells.
- The lack of response to vitamin D3 contrasts with previous findings, suggesting different mechanisms at play.
- Further research is needed to understand the pathways linking preeclampsia exposure to offspring cardiovascular disease risk.
Objectives:
Preeclampsia is one of the main contributers to maternal and fetal morbidity and mortality during pregnancy. A history of preeclampsia puts mother and offspring at an increased cardiovascular risk in later life. We hypothesized that at the time of birth functional impairments of fetal endothelial cells can be detected in pregnancies complicated by preeclampsia and that a therapeutic intervention using 1,25 (OH)2 vitamin D3 can reverse the adverse effects of preeclampsia on cell function.
Methods:
Human umbilical vein endothelial cells (HUVEC) were isolated from umbilical cords obtained from preeclamptic (N = 12) and uncomplicated pregnancies (N = 13, control). Placental villous tissue fragments from uncomplicated term pregnancies were incubated in explant culture for 48 h at 2% (hypoxia), 8% or 21% O2. Explant conditioned media (CM) was collected and pooled according to oxygen level. We compared the ability of preeclampsia vs. control HUVEC to migrate, proliferate, and form tubule-like networks in a Matrigel assay, in the presence/absence of CM and 1,25(OH)2 vitamin D3.
Results:
HUVEC from preeclamptic pregnancies showed reduced migration (P = 0.04) and tubule formation (P = 0.04), but no change in proliferation (P = 0.16) compared to healthy pregnancies. Placental villous explant CM derived from 2% O2 incubations significantly reduced HUVEC migration, when compared to non-CM (P = 0.04). Vitamin D3 improved HUVEC function in neither of the groups. There was no significant difference in VEGF gene expression between healthy and preeclamptic pregnancies and no effect of Vitamin D3 on VEGF expression.
Conclusions:
Reduced functional abilities of fetal endothelial cells from preeclamptic pregnancies suggests that disease pathways, possibly originating from the dysfunctional placenta, negatively impact fetal endothelium. The neutral effect of 1,25(OH)2 vitamin D3 contrasts with previous findings that vitamin D rescues the poor migration, proliferation and tubule formation exhibited by cord blood fetal endothelial progenitor cells from preeclamptic pregnancies. Further investigations to distinguish pathways by which offspring exposed to preeclampsia are at risk for cardiovascular disease are needed.
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