5 17-Hydroxyprogesterone caproate improves fetal growth restriction possibly by reducing sFlt-1 and placental cytolytic NK cells in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia

Abstract

Introduction Preeclampsia (PE), new onset hypertension, is characterized by decreased of nitric oxide (NO) 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. Objectives The objective of this study was determine whether early administration of 17-OHPC could improve pregnancy outcomes in response to placental ischemia. Methods. To do so, 17-OHPC (3.32 mg/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. Results 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 p 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 p p n = 5), which was blunted to 110.2 + 11.1 pg/mL in RUPP+17-OHPC, p n = 13) but was improved to 25.5 + 5.2 μM in RUPP + 17-OHPC ( n = 5), p Conclusion Early administration of 17-OHPC improves sFtl-1, UARI, activated cytolytic NK cells, pup weight, NO bioavailability and hypertension in response to placental ischemia. Therefore, 17-OHPC should be further considered for addition to the management of PE.