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181: Administration of 17-hydroxyprogesterone caproate in mid-gestation improves fetal growth possibly by reducing sFlt-1 and placental cytolytic NK cells in the Reduced Uterine Perfusion Pressure (RUPP) rat model of Preeclampsia

      Objective

      Preeclampsia (PE) is characterized by elevated anti-angiogenic factor soluble fms-like tyrosine kinase (sFlt-1), cytolytic natural killer (NK) cells and placental ischemia predicted with increased uterine artery resistance (UARI) which are likely culprits for decreased fetal weight during PE pregnancies. Cytolytic NK have been shown to be increased in PE women compared to those with normal pregnancy (NP). Currently, there is no effective treatment for PE except for delivery, making PE the leading cause for premature births worldwide. Administration of 17-hydroxyprogesterone caproate (17-OHPC) is used for prevention of spontaneous preterm labor, but is not included in the current management for PE. This study was designed to test the hypothesis that early administration of 17-OHPC could improve pregnancy outcomes in response to placental ischemia.

      Study Design

      17-OHPC (3.32mg/kg) was administered intraperitoneally on gestation day 15 to reduced uterine perfusion pressure (RUPP) rats, UARI was measured using Doppler ultrasound and carotid catheters were inserted on day 18. Blood pressure (MAP), sFlt-1, and placental cytolytic NK cells were measured on GD 19.

      Results

      MAP in normal pregnant (NP) rats (n=12) was 94 + 2, 126 + 2 in RUPP (n=27) and 111+1 mmHg in RUPP+17-OHPC (n=15), p <0.05. Pup weight was 2.3+0.09 in NP, 1.9+ 0.04 in RUPP rats, which improved to 2.1+0.06 grams in RUPP+17-OHPC p <0.05. UARI was 0.6+0.01 in NP (n=3), 0.8+0.03 in RUPP rats (n=4), which improved to 0.6+0.04 in RUPP+17-OHPC (n=5), p<0.05. Total number of placental NK cells was 8.6 + 3.1 in NP, 20.2 +2.4 in RUPP rats, which decreased to 1.6 + 0.54 % in RUPP+17-OHPC, p<0.05. Activated placental NK cells was 3.8 + 2.2 in NP, 11.9+2.01 in RUPP, which improved to 0.4 + 0.2 % in RUPP+17-OHPC, p <0.05. Plasma sFlt-1 was 36.1+7.5, 385.9+141 in RUPP rats (n=5), which was blunted to 110.2+11.1 pg/mL in RUPP+17-OHPC, p<0.05.

      Conclusion

      Mid-term administration of 17-OHPC improves sFtl-1, UARI, activated cytolytic NK cells, pup weight and hypertension in response to placental ischemia and could be considered for addition to the management of PE.