(944) Novel roles of ET-1 in superimposed preeclampsia

This study aims to determine if low maternal endothelin-1 (ET-1) expression causes preeclampsia-like phenotypes during pregnancy using mice with modified Edn1 alleles (L) that have ~30% of the wild type (WT) circulating ET-1 levels.

Study Design:

At 8-10 weeks of age, Edn1^L/L females were mated with Edn1^L/L males, and WT females were mated with WT males. One batch of dams from each group was sacrificed at 18.5 days post coitus (dpc) and maternal urine, plasma, and kidneys were collected. Urine albumin, and serum markers of preeclampsia—soluble fms-like tyrosine kinase 1 (sFlt-1), vascular endothelial growth factor (VEGF), and soluble endoglin (sENG)—were measured using ELISA kits. Electron microscopy of the glomeruli was examined at 18.5 dpc. A separate batch of dams from each group was reared through term delivery (19.5 to 21.5 dpc). Tail-cuff blood pressure measurement was performed on WT and Edn1^L/L female mice before pregnancy, at 13.5 dpc, at 17.5 dpc, and at 7 days postpartum.

Results:

Virgin Edn1^L/L females were hypertensive but did not demonstrate any other obvious abnormalities. Edn1^L/L females developed the full spectrum of preeclampsia-like phenotypes during pregnancy, including elevated systolic blood pressure and urinary albumin secretion, and glomerular endothelial damage. On the day of delivery, Edn1^L/L dams had fewer live neonates. At 18.5 dpc, Edn1^L/L dams also had fewer live fetuses and reduced fetal weight. The placental weights were not different between Edn1^L/L and WT dams. Interestingly, all serum markers of PE were lower in Edn1^L/L dams compared to WT dams.

Conclusion:

Our results show low maternal ET-1 expression causes preeclampsia-like phenotypes during pregnancy and leads to adverse pregnancy outcomes in mice.