The expression of deiodinase 2 and deiodinase 3 are reduced by insulin and D-glucose respectively, in human placental explant cultures

Abstract Introduction: Gestational diabetes mellitus is associated with altered expression of deiodinases (DIO), a group of seleno-enzymes that metabolize thyroid hormones in several tissues, including human placenta. It has been reported that these alterations could lead to reduced fetal thyroid hormone levels and impaired central nervous system development. However, it is not clear if D-glucose or insulin, which levels are increased in metabolic pathologies such as Gestational diabetes mellitus, are responsible for this phenomenon. Methods: We recruited 10 women with normal pregnancies from Hospital Guillermo Grant Benavente, Concepcion, Chile. After delivery, explants were extracted from placenta to perform cultures exposed to different concentrations of D-glucose and insulin, in order to evaluate deiodinase mRNA expression by RT-qPCR, enzymatic activity and protein localization by immunohistochemistry. Results: We observed that insulin could decrease both DIO2 mRNA (~38%) and activity (~40%), and D-glucose diminished DIO3 mRNA (~48%) as well as its activity (~36%). At control conditions DIO2 expression was observed mainly in fetal vasculature, while DIO3 expression focused on macrophage-like cells. D-glucose did not change deiodinase localization in placenta, whereas insulin promoted DIO2 and DIO3 expression in syncytiotrophoblast. Conclusion: We suggest that a diabetogenic state in pregnancy with high levels of D-glucose and insulin, may lead to deiodinase alterations in placenta and consequently fetal thyroid dysfunction.