Progesterone induced blocking Factor attenuates hypertension and placental mitochondrial dysfunction and reactive oxygen species in response to sFlt-1 during pregnancy
Jalisa Jones1, Evangeline Deer2, Kyleigh Comely2, Denise C. Cornelius2, Tarek Ibrahim2, Ramana Vaka2, Michael Franks2, Lorena M. Amaral2, Babbette LaMarca2
1Mississippi INBRE Research Scholar, Tougaloo College, Tougaloo, MS
2Pharmacology & Emergency Medicine University of Mississippi Medical Center, Jackson, MS
Preeclampsia (PE) is characterized by new onset hypertension in association with placental ischemia, reduced fetal weight, elevated soluble fms-like tyrosine kinase-1 (sFlt-1) and placental mitochondrial (mt) dysfunction and oxidative stress (ROS) during pregnancy. However, a role for sFlt-1 in causing mt dysfunction and ROS is unknown. Progesterone induced blocking factor (PIBF), is a product of progesterone signaling that we have shown to lower blood pressure in a rat model of PE. This study was designed to examine the role of mt mediated ROS in sFlt-1 induced hypertension during pregnancy as well as to determine the therapeutic effect of PIBF. sFlt-1 was infused into normal pregnant (NP) rats (3.7 μg·kg−1·day−1 on gestation days 13-19) in the presence or absence of PIBF (2.0 µg/mL) administered intraperitoneal on gestation day 15. Mean arterial blood pressure (MAP) and placental mt ROS were measured on gestation day 19. sFlt-1 increased MAP to 112 +2 (n=11) compared with NP rats 98+2 mmHg (n=15, p<0.05) which was reduced to 100+1 mmHg with PIBF (n=5, p<0.05). Mt ROS in placenta was 108+6 in NP (n=4), 429+32 in NP+ sFlt-1(n=3) and reduced to 234+15 in NP+ sFlt-1+ PIBF (n=3). Our study indicates placental mt dysfunction in sFlt-1 induced hypertension during pregnancy. Supplementation of PIBF improved placental mt function and blood pressures, indicating the importance of progesterone signaling as potential therapeutics for PE.