Reduced Placental Response to Oxidative Stress in Women with Gestational Diabetes Mellitus

Strategic Insights -

Researchers at the Baker Heart Research Institute in Melbourne, Australia, have found that the placenta in women with gestational diabetes mellitus (GDM) has a reduced capacity to respond to oxidative stress. This reduced response is mediated by nuclear factor-kappa B (NF-kappaB) activity. The study, published in the Journal of Clinical Endocrinology and Metabolism, found that under basal conditions, the release of proinflammatory cytokines was similar in both control and GDM groups. However, when exposed to oxidative stress, the response of GDM tissues was blunted, with no change in 8-isoprostane release, a four-fold increase in TNF-alpha release, and a 40% reduction in NF-kappaB DNA-binding activity.

Key Takeaways:

  • The placenta in women with gestational diabetes mellitus (GDM) has a reduced capacity to respond to oxidative stress, which is mediated by NF-kappaB activity.
  • Under basal conditions, the release of proinflammatory cytokines is similar in both control and GDM groups.
  • When exposed to oxidative stress, the response of GDM tissues is blunted, with an increased release of TNF-alpha and a reduction in NF-kappaB DNA-binding activity.
  • This reduced response to oxidative stress may contribute to the pathogenesis of GDM and other metabolic events, including decreased insulin sensitivity.
  • The study suggests that pre-exposure and/or adaptation to oxidative stress by GDM tissues may be responsible for the differences in ex situ release of proinflammatory cytokines from placental and adipose tissues.
  • The researchers propose that the blunted response of GDM tissues to oxidative stress may be a result of repression of NF-kappaB activity.

Statistics:

  • The release of TNF-alpha and 8-isoprostane was two-fold greater in the GDM group compared to the normal group under basal conditions.
  • In response to oxidative stress, TNF-alpha release was increased four-fold, and NF-kappaB DNA-binding activity was reduced by 40% in the GDM group.
  • The study found that the response of normal tissues to oxidative stress was significantly increased, with a 20-fold increase in TNF-alpha release, a 2-fold increase in 8-isoprostane release, and a 35% increase in NF-kappaB DNA-binding activity.

Sources:

  • Coughlan, M.T., et al. (2004). Repression of oxidant-induced nuclear factor-kappa B activity mediates placental cytokine responses in gestational diabetes. J Clin Endocrinol Metab, 89(7), 3585-3594.
  • Baker Heart Research Institute. (n.d.). Danielle Alberti Memorial Center for Diabetes Complications. Retrieved from
  • Endocrine Society. (n.d.). Journal of Clinical Endocrinology and Metabolism. Retrieved from