Abstract 61: Cd4+t Cells Cause Hypertension, Increased Glucose, And Mitochondrial Dysfunction In A Novel Rodent Model Of Gestational Diabetes Mellitus

Abstract

Hypertensive (HTN) disorders of pregnancy increase risks for gestational diabetes mellitus (GDM) in pregnant women. GDM is characterized by hyperglycemia and β-cell dysfunction associated with increased inflammatory cytokines, oxidative stress, and activated CD4+ T cells. Streptozotocin (STZ) is used in nonpregnant rats to induce β-cell destruction causing features of diabetes. However, STZ is not ideal for pregnancy and leads to unsuccessful pregnancy outcomes, therefore other ways to establish animal models of GDM must be pursued. Previously, we showed CD4+T cells from a rat model of preeclampsia causes HTN and mitochondrial (mt) dysfunction/ROS compared to normal pregnant (NP) rats. Therefore, we hypothesize CD4+ T cells from a diabetic rat model could cause mt dysfunction/ROS and pancreatic β-islet cell destruction and lead to increased glucose and HTN during pregnancy. To examine our hypothesis, we adoptively transferred CD4+ T cells from STZ Dahl diabetic rats into pregnant Sprague Dawley (SD) rats and measured GDM features. Circulating CD4+ T cells were isolated from STZ induced diabetic Dahl virgin female rats and injected into pregnant SD rats on gestational day (GD) 12. On GD19, blood pressure (MAP) and tissues were collected and glucose levels were measured after 2h fasting in STZ CD4+ T cell recipients (GDM) and NP controls. Mt respiration and mtROS was measured in isolated mitochondria. On GD19, MAP increased to 105±0.5 mmHg (n=4, p<0.05) in GMD pregnant rats compared to control NP rats 91±2.1 mmHg (n=3). Blood glucose levels were elevated in GDM rats (139 ± 7 mg/dl, n=4, p<0.05) compared to NP controls (94 ± 1 mg/dl, n=3). Placental state 3 (26.4±5.9 vs 53.9±1.7 pmol/sec/mg, p<0.05) respiration rates, indicative of ATP production, was reduced in GDM rats (n=4) compared to NP controls (n=3). Placental mtROS was significantly increased in GDM rats (190 ± 27.1 % gated, n=3, p<0.05) compared to NP rats (100 ± 2.7 % gated, n=3). Collectively, the data indicate adoptive transfer of STZ CD4+ T cells causes increased circulating glucose, placental mt dysfunction and mtROS and HTN during pregnancy. These data demonstrate the importance of CD4+T cells in mechanisms causing the pathophysiology of GDM, and also introduces a potential novel animal model of GDM.