Progesterone induced blocking factor improves fetal growth restriction possibly by reducing inflammation and placental cytolytic NK cells in response to placental ischemia during pregnancy

Preeclampsia (PE), new onset hypertension, is a progesterone deficient state and is associated with an imbalance among CD4 + T lymphocytes, natural killer (NK) cells, and inflammatory cytokines which are likely culprits for decreased fetal weight during PE pregnancies. During normal pregnancy activated lymphocytes express progesterone receptors, which enable progesterone to induce a protein called progesterone induced blocking factor (PIBF). PIBF increases during normal pregnancy and has been shown to decrease inflammation and cytolytic NK cells, both of which are increased during PE. Currently, there is no effective treatment for PE except for early delivery, making PE the leading cause for premature births worldwide. We have previously shown that progesterone supplementation with 17‐OHPC improves inflammation, fetal weight and blood pressure in the preclinical RUPP rat model of PE. However the mechanism where by progesterone improves the pathophysiology of PE has never been determined. This study was designed to test the hypothesis that PIBF reduces inflammation while improving hypertension in response to placental ischemia. To test this hypothesis, PIBF (2.0 μg/mL) was administered intraperitoneally on gestation day 15 to RUPP or normal pregnant (NP) rats and on day 18 carotid catheters were inserted and on GD 19 blood pressure and samples were collected. MAP in NP rats (n=9) was 102± 3 and 110 ± 3 in NP+PIBF (n=5), 124± 3 in RUPP rats (n=4), which improved to 110±3 mmHg in RUPP+PIBF (n=8), p<0.05. Pup weight was 2.4± 0.1 g in NP, 2.5± 0.1 in NP+PIBF, 1.9±0.1 in RUPP and improved to 2.2±0.1 in RUPP+PIBF, p<0.05. Total placental NK cells were 31± 9 in NP (n=4), 31±5 in NP+PIBF (n=4), 42 ±8 in RUPP rats (n=4) and reduced to 26± 2 in RUPP+PIBF (n=6). Placental cytolytic NK cells were 0.8±0.1 in NP, 0.2±0.1 in NP+PIBF, and 1.4±0.1 in RUPP rats, which decreased to 0.4+0.1 in RUPP+PIBF, p<0.05. CD4 + T cells were decreased from 21±6 in RUPP rats (n=4) to 8±2 gate in RUPP+PIBF (n=7). Collectively, our findings demonstrate that PIBF, a produce to progesterone receptor stimulation by progesterone, could be a mechanism to improve fetal growth restriction, inflammation as indicated by CD4+ T cells and cytolytic NK cells while normalizing blood pressure in response to placental ischemia during pregnancy. Support or Funding Information Supported by NIH grants RO1HD067541, HL130456 and AMAG Pharmaceuticals This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .