Progesterone Supplementation Reduces AT1-AA, Inflammation and Blood Pressure in Response to Preeclamptic Placental CD4+ T Cells in Pregnant Nude-Athymic Rats

Introduction: Preeclampsia (PE) is characterized by new onset hypertension after 20 weeks of gestation. It affects 5-7% of all pregnancies in the U.S.A, and is associated with activated CD4+T cells, inflammation, autoantibodies to angiotensin II type 1 receptor (AT1-AA), reduced fetal weight and hypertension. The mechanisms responsible for the pathogenesis of PE are unclear and currently the only treatment is early delivery of the feto-placental unit. We have previously shown that CD4+ T cells adoptive transfer causes a PE phenotype in athymic nude rats. Objective: Determine whether progesterone, in the form of 17-hydroxyprogesterone caproate (17-OHPC), attenuates the effect of placental PE CD4+ T cells to cause signs of PE in athymic nude rats. Methods: One million of placental CD4+ T cells from normal pregnant (NP) or PE participants were isolated by magnetic separation and injected I.P. into pregnant nude athymic rats on gestational day (GD) 12. On GD 15, 17-OHPC (3.32mg/kg) was administered I.P. On GD18, carotid catheters were inserted. On GD19, mean arterial blood pressure, blood and tissues were collected. Participants whose placental CD4+ T cells were used in this study had matched gestational age. A student’s t-test or one-way ANOVA were used for statistical analysis. All data are expressed as mean ± standard error means (SEM). Results: Blood pressure was 116+/-4 in NP (n=8), 147 +/- 4 mmHg in PE group (n=19) and significantly reduced to 136 +/- 3 mmHg in PE+17-OHPC group (n=14, p<0.05). CD4+ T cells were 2+/- 1 % gate in NP, 6 +/- 1 in PE, and 3 +/-1 % gate in PE+17-OHPC group (n= 5). TNF-alpha were 21 +/- 4 pg/mL in NP(n=6),41 +/-8 in PE group (n=8), and reduced to 21+/-5 in PE+17-OHPC (n=6, p<0.05). AT1-AA levels were 23 +/- 5 ΔBPM (beats per minute) in PE group (n=4) and 10/-2 in PE+17-OHPC group (n=8). MAP was 98 +/- 2 mmHg in NP CD4+ T cells rats (n=5), 81+/-2 in NP CD4+ Tcells+17-OHPC (n=5), 124 +/- 5 mmHg in PE CD+4 T cells (n=9), which decreased to 103 +/- 4 mmHg in PE CD4+ T cells+17-OHPC (n=10). Pup weight was 1.8+/- 1 grams in PE CD+4 T cells, which increased to 2.2 +/- 1 grams mmHg in PE CD4+ T cells+17-OHPC (p<0.05). AT1-AA were -3 +/- 2 Δ beats per minute (BPM) in NP CD4+ T cells group, 8+/-2 ΔBPM in PE CD+4 T cells (n=4). 17-OHPC treatment significantly decreased to -6 +/- 1 ΔBPM (n=3, p<0.05). Conclusion: CD4+ T cells play an important role in the pathophysiology of preeclampsia and 17-OHPC reduces the signs of PE in pregnant nude-athymic rats. Supported by NIH P20GM121334 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.