Abstract 014: Gestational Diabetic Cd4+ T Cells Cause Increased Glucose, Blood Pressure And Placental Mitochondrial Dysfunction In A Novel Rat Model Of Diabetes During Pregnancy

Abstract

Hypertensive (HTN) disorders complicate ~10% of all pregnancies worldwide and contribute to maternal and fetal morbidity and mortality. HTN increases risks for preeclampsia and preterm labor in women with gestational diabetes mellitus (GDM) and is characterized by hyperglycemia resulting from defects in insulin activity/secretion or both. Also, increased levels of maternal glucose, inflammatory mediators, abnormal placental vascular function, and cytokines are associated with the pathogenesis of GDM, however, we don’t know the importance of placental factors, inflammatory cells, and cytokines in causing HTN or other pathophysiological factors associated with GDM. We hypothesize placental CD4+T cells from pregnant DM patients (GDM) causes a DM phenotype in pregnant athymic nude rats. CD4+T cells were magnetically separated from placentas from GDM patients and injected into athymic nude rats on Gestation Day (GD) 12. On GD19, blood pressure (MAP), blood and tissues were collected and glucose was measured from GDM CD4+T cell recipients and pregnant nude control rats.Mitochondrial respiration and mtROS were measured as indicators of tissue function from isolated placental mitochondria using the Oxygraph 2K and fluorescent microplate reader, respectively. A student’s t-test was used for statistical analysis. On GD19, MAP increased to 117±5.3 mmHg (n=3) in GDM T cell recipients compared to control pregnant athymic nude rats 102±0.0 mmHg (n=5). Blood glucose levels were elevated with GDM CD4+ T cells (275 ± 80 mg/dl, n=3, p<0.05) compared to pregnant athymic nude rats (91 ± 16 mg/dl, n=5).Placental state 3 (10±1 vs 433±113 pmol/sec/mg, p<0.05), indicative of ATP production, was reduced with GDM CD4+ T cells (n=3) compared to control pregnant athymic nude rats(n=5). Placental mtROS (H2O2) was increased with GDM CD4+ T cells (264 ± 14 % gated, n=3, p<0.05) compared to pregnant athymic nude rats (100 ± 26 % gated, n=5).Collectively, these data indicate that GDM CD4+T cells cause the GDM phenotype during pregnancy by increasing glucose and blood pressure in association with placental mitochondrial dysfunction/ROS during pregnancy, thereby introducing a new model to investigate mechanisms and new therapies for diabetes during pregnancy.