Gestational diabetes (GD) is a common pregnancy-related disorder, coupled with altered placental vascular reactivity and has severe consequences for fetal growth. Our previous findings revealed a potentially safe hypoglycemic action of Cinnamaldehyde (Ci) on a rat-model that mimics human GD-pathophysiology. This study aims to provide an integrated approach to unravel placental responses to GD through transcriptional, biochemical and histopathological analyses and how Ci mitigates these effects in comparison to glyburide/metformin-HCl (Gly/Met).
We used the fatty-sucrosed diet/streptozotocin (FSD/STZ)-rat model of GD. Oral doses of Ci (20 mg/kg) or Gly/Met (0.6+100 mg/kg) were given daily, from one week before mating onwards. On day 20 of pregnancy, maternal and fetal blood was collected for glucose, insulin, erythropoietin (EPO) and hematocrit (Hct) measurements. Placentae were taken for transcriptome, metabolite and enzymatic antioxidant profiling. Also, H&E and PAS-staining were used for histopathological assessments. Fetal liver was excised for iron content evaluation.
Fetuses of GD-group showed a significant drop in Hct level, a 4-fold increase in serum-EPO and 28% reduction of their liver-iron content compared to controls, which indicates fetal hypoxia. Interestingly, both Ci and Gly/Met reduce GD-hyperglycemia but only Ci mitigates fetal hypoxia. Placental transcriptomic changes of diabetic and Gly/Met-treated groups revealed overrepresented pathways of angiogenesis, response to hyperoxia and reactive oxygen species biosynthesis with evidences of O2-consumption for glucose oxidation. Biochemical assays confirmed these findings. Additionally, Ci prevents distinct structural alterations of diabetic placenta that predominantly include labyrinth hypervascularization and glycogen increment.
Ci counteracts GD-induced fetal hypoxia by improving placental function.