Gestational diabetes mellitus in women increased the risk of neonatal infection via inflammation and autophagy in the placenta.

Abstract

Gestational diabetes mellitus (GDM) produces numerous problems for maternal and fetal outcomes. However, the precise molecular mechanisms of GDM are not clear. In our study, we randomly assigned 22 pregnant women with fasting glucose concentrations, 1 hour oral glucose tolerance test (1H-OGTT) and 2 hour oral glucose tolerance test (2H-OGTT), different than 28 normal pregnant women from a sample of 107 pregnant women at the First Affiliated Hospital of Jinan University in China. Lipopolysaccharide (LPS), interleukin 1 alpha (IL-1α), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-α) were measured from blood plasma of pregnant women and umbilical arteries using ultraviolet spectrophotometry. Hematoxylin & Eosin (H&E), Periodic acid-Schiff (PAS) or Masson staining were performed to examine whether diabetes mellitus altered the morphology of placenta. Quantitative PCR (Q-PCR), western blotting and immunofluorescent staining were performed to examine whether diabetes mellitus and autophagy altered the gene expressions of the placental tissue. We found that women with GDM exhibited increased placental weight and risk of neonatal infection. The concentrations of IL-6 protein and IL-8 protein in GDM were increased in both maternal and umbilical arterial blood. H&E, Masson and PAS staining results showed an increased number of placental villi and glycogen deposition in patients with GDM, but no placental sclerosis was found. Q-PCR results suggested that the expression levels of HIF-1α and the toll like receptor 4 (TLR4)/ myeloid differential protein-88 (MyD88)/ nuclear factor kappa-B (NF-κB) pathway were increased in the GDM placenta. Through Western Blotting, we found that the expression of NF-kappa-B inhibitor alpha (IKBα) and Nuclear factor-κB p65 (NF-κB p65) in GDM placenta was significantly enhanced. We also showed that the key autophagy-related genes, autophagy-related 7 (ATG7) and microtubule-associated protein 1A/1B-light chain 3 (LC3), were increased in GDM compared with normal pregnant women. Our results suggest that women with GDM exhibit an increased risk of neonatal infection via inflammation and autophagy in the placenta.