Basic Science
Poster Session 3
Danielle Frieson, MD, MS (she/her/hers)
Fellow
University of Mississippi Medical Center
Jackson, MS, United States
Jan Michael Williams, PhD
University of Mississippi Medical Center
Jackson, MS, United States
Jean Vel, MD
Fellow
University of Mississippi Medical Center
Madison, MS, United States
Baoying Zheng, MS
University of Mississippi Medical Center
Jackson, MS, United States
Mariah Wilson, BS
University of Mississippi Medical Center
Jackson, MS, United States
Nathan Campbell, BS
University of Mississippi Medical Center
Jackson, MS, United States
Babbette LaMarca, PhD
Professor, Chair
University of Mississippi Medical Center
Jackson, MS, United States
Evangeline Deer, PhD (she/her/hers)
Instructor
University of Mississippi Medical Center
Jackson, MS, United States
Gestational diabetes mellitus (GDM) refers to glucose intolerance, insulin sensitivity and beta islet cell dysfunction during pregnancy. GDM pathogenesis is associated with hypertension, impaired placental and renal function, oxidative stress and increased circulating CD4+ T cells. Importantly, there are limited animal models available to explore GDM pathology and treatment. This study sought to determine a role for GDM patient placental CD4+ T cells to parallel the manifestations of GDM phenotype in pregnant athymic nude recipient rats.
Study Design: GDM placental CD4+ T cells (GDM-CD4+ T cells) were magnetically isolated upon delivery and injected into pregnant nude athymic rats on gestational day (GD) 12. Mean arterial pressure (MAP) and markers of renal injury, proteinuria, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) and placental mtROS were assessed on GD19. Glucose and Glucose tolerance tests (GTT) were performed on GD 19. Renal and pancreatic tissues were stained for Periodic acid Schiff (PAS) and hematoxylin and eosin (H&E). A student’s t-test was used for statistical analysis.
Results:
On GD19, MAP was higher in GDM-CD4+ T cell rats (121±3, n=8, p< 0.05) compared to pregnant athymic nude control rats (105±3 mmHg, n=8). Blood glucose was 201±46 mg/dl, (p< 0.05) in GDM CD4+T cell rats compared pregnant controls (82±9 mg/dl). GTT was impaired in GDM CD4+ T rats. Proteinuria and markers of renal injury were elevated in GDM-CD4+ T cell rats (5±0.8 ml/day (p< 0.05);47±10 pg/mg, (p< 0.05); 28±4 pg/mg, (p< 0.05)) compared to controls (2±0.3 ml/day;22±3 pg/mg; 12±1 pg/mg). Histological analysis showed increased glomerular damage and decreased beta islet number in GDM-CD4+T cell rats compared to controls. Placental mt ROS increased in GDM CD4+ T cells rats (291±47 FLU, p< 0.05) compared to controls (100±18 FLU).
Conclusion: Our findings indicate that GDM CD4+ T cells cause a diabetic phenotype during pregnancy suggesting a new model to investigate mechanisms and therapies for diabetes during pregnancy.