Abstract 076: Early Administration of 17-hydroxyprogesterone Caproate Improves Fetal Growth Restriction Possibly by Reducing Sflt-1 and Placental Cytolytic Nk Cells in Response to Placental Ischemia During Pregnancy

Abstract

Preeclampsia (PE), new onset hypertension, 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 are an important arm of the immune system killing tumor and infected cells by perforin-granzyme-mediated cytolysis and have been shown to be increased in PE women compared to those with normal pregnancy. Currently, there is no effective treatment for PE except for early 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. To do so, 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. 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. In conclusion, early administration of 17-OHPC improves sFtl-1, UARI, activated cytolytic NK cells, pup weight and hypertension in response to placental ischemia. Therefore, 17-OHPC should be further considered for addition to the management of PE.