Early Administration of 17- Hydroxyprogesterone Caproate Improves Pathophysiology in RUPP Rats

Undergraduate #122
Discipline: Biological Sciences
Subcategory: Physiology and Health

Jessica McKenzie - Tougaloo College
Co-Author(s): Lorena M. Amaral, Jessica L. Faulkner, Denise C. Cornelius, Janae Moseley, James N. Martin, and Babbette LaMarca, University of Mississippi Medical Center, Jackson, MS

---

Preeclampsia is characterized by blood pressure greater than 140/90 mmHg after the 20th week of gestation with proteinuria. Preeclampsia also causes increased uterine artery resistance, elevated tumor necrosis factor-α, enhanced of the antiangiogenic factor sFlt-1, and decreased of nitric oxide bioavailability during pregnancy. 17- Hydroxyprogesterone (17OHPC) is already used in prevention of pre-term labor without preeclampsia complications. Therefore, we hypothesized that early administration of 17-hydroxyprogesterone caproate on day 15 of gestation in RUPP rats could improve pathophysiology in response to placental ischemia during pregnancy such as blood pressure (MAP), TNF-α, sFlt-1, UARI, and a increase pup weight and NO bioavailability. Carotid catheters were inserted on day 18 and the uterine artery resistance index was measured using Doppler Ultrasound. Blood pressure, blood and tissues were collected on day 19. MAP in normal pregnant (NP) rats (n=9) was 92 +1.35, 126 +1.98 in RUPP rats (n=17) and 111+1.54 mmHg in RUPP+17-OHPC (n=13), p <0.05. Pup weight was 2.31+0.12 in NP (n=13), 1.88+ 0.05 in RUPP rats (n=24), which improved to 2.01+0.07 grams in RUPP+17-OHPC (n=15), p <0.05. UARI was 0.79+0.03 in RUPP rats (n=4) and 0.59+0.04 in RUPP+17-OHPC(n=5), p<0.05. Plasma levels of TNF-α, sFlt-1 were 64.0+14.1, 385.9+141 in RUPP rats (n=7), which were blunted to 17.8+9.6, 110.2+11.1pg/mL in RUPP+17-OHPC (n=5),p<0.05. Plasma NOx was 10.82+2.3 in RUPP rats (n=13) but was improved to 25.5+5.2 µM in RUPP+17-OHPC (n=5), p<0.05. In conclusion, early administration of 17-OHPC improves inflammation, sFtl-1, Uterine Artery Resistance Index, hypertension, pup weight and nitric oxide bioavailability in response to placental ischemia, and therefore should be considered further for addition to the clinical management of preeclampsia.

Funder Acknowledgement(s): NIH grant RO1HD067541, NIH grant T32HL105324

Faculty Advisor: Babbette LaMarca,