Expression of placental hypoxia-inducible factor-1α and vascular epithelial growth factor in gestational diabetes mellitus and relationship with pregnancy outcomes

Abstract

Objective To investigate the expression of placental hypoxia-inducible factor-1α (HIF-1α) and vascular epithelial growth factor (VEGF) in gestational diabetes mellitus (GDM) and its correlation with placental histological abnormalities and GDM pregnancy outcomes. Methods A case-control study was performed in 44 women with GDM, including 10 cases with not well-controlled glucose level (group A) and 34 cases with well-controlled glucose level (group B), and 37 healthy pregnant women (group C) with 36-41 pregnancy weeks and delivered between October 2010 to October 2011 Placental tissue was histologically examined by HE staining method. The protein expression of HIF-1α and VEGF in placenta was detected by immunohistochemistry. The expression of HIF-1α and VEGF mRNA in placenta was detected by RT-PCR, to compare the differential expression of HIF-1α and VEGF between three groups, and its relationship with pregnancy outcomes.Data was compared using Pearson correlation. P values <0.05 were considered statistically significant. Results (1) Women in group A were more likely to develop gestational hypertension, postpartum hemorrhage, polyhydramnios, premature delivery, macrosomia delivery and neonatal hypoglycemia delivery than other groups (P<0.05). (2) The presence of villous immaturity, vascular thickening and intervillous capillary enlargement was significantly increased in the placenta of GDM (P<0.05). (3) The expression of HIF-1α and VEGF mRNA in group A (0.91±0.13 and 0.96±0.23, respectively) and B (0.72±0.12 and 0.75±0.27, respectively) was significantly more than which in group C (0.47±0.11 and 0.43±0.14, respectively, P<0.05). (4) The protein of HIF-1α and VEGF was expressed in all groups. The protein expression of HIF-1α and VEGF in group A (90.0% and 100%, respectively) and group B (82.4% and 88.2%, respectively) was significantly more than which in group C (32.4% and 35.1%, respectively, P<0.05). (5) The protein expression of HIF-1α and VEGF in GDM groups was positively correlated with the presence of villous immaturity (r=0.764, 0.875, respectively, P<0.05), stem villus arteriole thickening (r=0.655, 0.885, respectively, P<0.05) and intervillous capillary congestion (r=0.685, 0.766, respectively, P<0.05). Conclusions Over-expression of HIF-1α and VEGF in GDM placenta may be related to the placenta angiogenesis and maturation abnormalities, which is associated with adverse pregnancy outcomes of GDM. Key words: Gestational diabetes mellitus; Placenta; Hypoxia-inducible factor-1α; Vascular epithelial growth factor