ANTIOXIDANT TREATMENT RESCUES THE HYPERGLYCEMIC AND HYPERLIPIDEMIC EFFECTS ON PLACENTAL IRON HOMEOSTASIS

Zaugg, Jonas; Zurkinden, Line; Melhem, Hassan; Kalakaran, Thuvaraga; Albrecht, Christiane (2019). ANTIOXIDANT TREATMENT RESCUES THE HYPERGLYCEMIC AND HYPERLIPIDEMIC EFFECTS ON PLACENTAL IRON HOMEOSTASIS. Placenta, 83, e93-e93. Elsevier

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Objectives: We have previously demonstrated an association between
gestational diabetes mellitus and dysregulated placental iron transport
and regulation. In this context we aimed to investigate the effect of antioxidant
treatment to counterbalance the pathophysiological effects of
elevated glucose and lipid levels on placental iron homeostasis.
Methods: In newly established BeWo-derived cell models, we assessed the
time-dependent adaption of trophoblast cells to normoglycemic, hyperglycemic
and hyperglycemic combined with hyperlipidemic conditions.
During 5 weeks we monitored iron uptake, expression patterns of iron
transporters and regulators and cellular responses involving autophagy and
oxidative stress pathways. Autophagy markers were analyzed by immunoblotting
and oxidative stress by TBARS, total GSH and protein carbonylation
assays. In parallel, selenium (Se) supplementation was applied to
assess and counteract oxidative stress levels induced by hyperglycemia/
hyperlipidemia. Using qRT-PCR we analyzed 7 genes involved in placental
iron homeostasis. The gene expression results were complemented by
protein data applying a newly developed mass spectrometry-based method.
Results: Elevated glucose levels in BeWo cells altered cellular morphology,
affected mRNA and protein expression of iron transporters and regulators,
and also reduced iron uptake confirming an impact of hyperglycemia on
placental iron transport function. Our results further indicated that
increased oxidative stress and changes in the autophagy pathway were
involved in altering iron homeostasis under hyperglycemic conditions.
Increased antioxidative potential through Se-supplementation was able to
completely rescue the adverse effects of hyperglycemia/hyperlipidemia on
iron homeostasis.
Conclusion: Our data indicate that changes in expression, localization and
function of placental iron transporters are responsible for reduced
placental iron transport under hyperglycemic conditions. These adaptations
could be part of a protective mechanism preventing oxidative damage
for both the fetus and the placenta caused by highly oxidative iron. The
successful rescue by Se supplementation suggests that antioxidant treatment
could protect pregnant women with increased risk to develop GDM
by balancing placental oxidative stress levels.

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