Histopathological and Immunohistochemical Changes in Placentas of Women with Gestational Diabetes Mellitus: CD56 and VEGF Expression

Abstract

Background: Gestational diabetes mellitus (GDM) is an increasingly prevalent metabolic disorder that can adversely affect both maternal and neonatal outcomes. The placenta is a key target organ in GDM, where metabolic and vascular disturbances may cause structural alterations and altered expression of angiogenic and immune-related markers. This study evaluated placental histopathological changes and the immunohistochemical expression of vascular endothelial growth factor (VEGF) and CD56 in pregnancies complicated by GDM.
Methods: This prospective comparative study included 120 pregnant women: 60 with GDM and 60 normoglycemic controls. GDM was diagnosed at 24–28 weeks of gestation. Maternal age, gestational age, parity, placental weight, and placental diameter were recorded. Placental specimens underwent routine histopathological examination and immunohistochemical staining for VEGF and CD56.
Results: Placentas from the GDM group showed multiple histopathological alterations, including villous overcrowding, decreased terminal-villus density, increased immature intermediate villi and terminal-villus size, increased syncytial knots, thickening of the villous basement membrane and villous vessels, cytotrophoblastic prominence, fibrinoid deposition and necrosis, fibrosis, increased Hofbauer cells, calcification, chorangiosis, fetal vascular thrombosis, nucleated fetal red blood cells, and villous edema. VEGF expression was significantly higher in GDM placentas than in controls, with moderate-to-strong immunoreactivity in syncytiotrophoblasts, villous stromal cells, and endothelial cells. In contrast, CD56 expression showed no statistically significant difference between the GDM and control groups.
Conclusion: GDM is associated with substantial placental histopathological alterations and increased placental VEGF expression, indicating disturbed placental vascular adaptation and angiogenesis. CD56 immunoexpression was not significantly altered in the placental tissue examined. Further studies that include the decidua basalis or placental bed and assess earlier gestational ages may better define the role of CD56-positive uterine natural killer cells in GDM. CD56-positive uterine NK cells are especially prominent in early decidua and participate in spiral-artery remodeling, which helps explain why they may be limited in term villous placental samples.