17-Hydroxyprogesterone caproate improves T cells and NK cells in response to placental ischemia; new mechanisms of action for an old drug

Jamil T. Elfarra, Jesse N. Cottrell, Denise C. Cornelius, Mark W. Cunningham, Jessica L. Faulkner, Tarek Ibrahim, Babbette Lamarca, Lorena M. Amaral

Research output: Contribution to journalArticlepeer-review

Abstract

Preeclampsia (PE) is new onset hypertension during pregnancy associated with increased uterine artery resistance (UARI) and an imbalance among CD4 + T lymphocytes and natural killer (NK) cells. We have shown an important role for 17-hydroxyprogesterone caproate (17-OHPC) to improve hypertension and fetal demise in the RUPP rat model of PE. However we have not examined a role for 17-OHPC to improve NK cells and CD4+TH2 cells as possible mechanisms for improved fetal weight and hypertension. Therefore, we hypothesized that 17-OHPC lowers NK cells while improving the T cell ratio in the RUPP rat. RUPP was surgically induced on gestational day 14 in pregnant rats. 17-OHPC (3.32 mg/kg) was administered intraperitoneal on day 15, UARI was measured on day 18. Blood pressure (MAP), blood and tissues were collected on GD 19. MAP in NP rats (n = 9) was 100 ± 2, 104 ± 6 in Sham rats (n = 8), 128 ± 2 in RUPP (n = 11) and 115 ± 3 mmHg in RUPP + 17-OHPC (n = 10), p < 0.05. Pup weight and UARI were improved after 17-OHPC. Total and cytolytic placental NK cells were 38 ± 5, and 12 ± 2% gate in RUPP rats which decreased to 1.6 ± 0.5 and 0.4 ± 0.2% gate in RUPP + 17OHPC rats. CD4+ T cells were 40 ± 3 in RUPP rats, which significantly decreased to 7 ± 1 RUPP + 17-OHPC rats. Circulating and placental TH2 cells were 6.0 ± 1, 0.3 ± 0.1% gate in RUPP rats and 12 ± 1%, 2 ± 0.5% gate in RUPP + 17-OHPC rats, p < 0.05 This study identifies new mechanisms whereby 17-OHPC improves outcomes in response to placental ischemia.

Original languageEnglish (US)
Pages (from-to)226-232
Number of pages7
JournalPregnancy Hypertension
Volume19
DOIs
StatePublished - Jan 2020

Keywords

  • 17-Hydroxyprogesterone caproate
  • Natural killer cells
  • Preeclampsia
  • Progesterone

ASJC Scopus subject areas

  • Internal Medicine
  • Obstetrics and Gynecology

Fingerprint

Dive into the research topics of '17-Hydroxyprogesterone caproate improves T cells and NK cells in response to placental ischemia; new mechanisms of action for an old drug'. Together they form a unique fingerprint.

Cite this