Endocrine Abstracts

Introduction: Formation of immunological tolerance to self antigens is an important mechanism that prevents the development of autoimmune diseases.

Methods: With the help of molecular genetic and immunofluorescence techniques we investigated the effects of experimental gestational diabetes (EGD) on the level of mRNA expression of autoimmune regulator Aire and differentiation features of Foxp3⁺ cells in mesenteric lymph nodes in the offspring of Wistar rats. To determine the level of Aire mRNA was performed RT-PCR in real-time by thermocycler CFX96 Real-Time PCR Detection Systems. The relative level of gene expression were studied with rat reference genes GAPDH by the method ΔΔCt. Statistical analysis were conducted using available software ‘Bio-Rad CFX Manager 3.1’ (Bio-Rad, USA). The immunopositive Foxp3+-lymphocytes were determined using an indirect immunofluorescence technique with using a monoclonal rat antibody.

Results: The offspring of EGD rats showed a reduction of autoimmune regulator Aire mRNA in 2,3-8,1 times (P<0.05) in MLN cells compared to control animals. The observed decrease in the transcriptional activity of Aire is accompanied by reduction in the number of regulatory Foxp3⁺ lymphocytes in MLN in the offspring of rats with EHD, as well as reduction of concentration of the transcription factor Foxp3 in lymphocytes of cortical plateau.

Conclusions: The revealed changes evidence of abuse of formation of peripheral immunological tolerance and can trigger the development of AID in the offspring of mothers with EHD.