Altered placental morphology and VEGF expression in diabetic rats

Diabetes is a common problem in approximately 7.6% of pregnant women older than 20 years in Brazil. Results from human and rodent diabetic experimental models have suggested that the placenta is a compromised target, which largely suffers the impact of maternal diabetes. In view of the importance of diabetes for maternal and neonatal health, the objective of the present study was to assess maternal glycemia and body weight, placental morphology and VEGF distribution in the rat animal model for diabetes that shows a similar placental phenotype observed in human diabetic pregnancy. Diabetes was induced by a single injection of alloxan in saline solution on gestational day (gd) 8 in Wistar rats. On 17 gd, rats from control (n=5) and diabetic (n=5) groups were anesthetized, exsanguinated, and laparotomized to remove the uterine horns for weighing of fetuses and placenta collection. Placentas were sampled and processed for paraffin embedding, histological and immunohistochemical analysis. The female rats showed severe diabetes (329.3 ± 13.38 mg/dl), but the maternal weight was not different between the two groups (control: 209.4 ± 11.08 g, diabetic: 198.2 ± 8.76 g). Placentas from the diabetic group had an enlarged junctional zone (JZ) and a straight arrangement of fetal capillaries and maternal sinusoids in the labyrinth zone (LZ). VEGF expression was observed in different cell types in the JZ and LZ. A greater number of glycogen and trophoblast giant cells positive for VEGF were quantified in the diabetic group. In the LZ, more cells were positive for VEGF in the control group than in the diabetic group. Severe hyperglycemia increased the expression of VEGF in the JZ and decreased in the LZ. The morphological changes in the size and organization of the spongiotrophoblast and glycogen cells in rat models of diabetes suggests the JZ as the placental compartment most sensitive to diabetes condition. Moreover, the VEGF role in the JZ is not fully understood and may have another function other than capillary growth.