EXPERIMENTAL GESTATIONAL DIABETES DISRUPTS THE FORMATION OF IMMUNE TOLERANCE IN OFFSPRING

The aim: To analyze the mRNA gene expression level of Aire, Deaf1, Foxp3, Ctla4, Il10, Nlrp3 and distribution of NLRP3+-cells in mesenteric lymph nodes (MLNs) of the offspring of rats with GD, both untreated and treated with glibenclamide and in conditions of insulin oral tolerance formation.

Materials and methods: The study involves 160 male rats, one- or six-month-old. The mRNA genes expression was studied by real time quantitative poly¬merase chain reaction. Structure of Nlrp3+ -cells population was studied by histological sections of MLNs.

Results: We observed AIRE gene repression, reduced mRNA levels of Deaf1 and the transcription factor Foxp3 in offspring of rats with GD. This was accompanied by inhibition of IL-10 gene expression and negative costimulatory molecules Ctla4. The development of the experimental GD was accompanied by transcrip¬tional induction of the Nlrp3 gene in MLNs of descendants. The administration of glibenclamide to pregnant female rats with GD inhibited the transcription of the Nlrp3 gene only in one-month-old offspring (5.3-fold) and did not change it in six-month-old animals. In offspring of rats with GD, the density of the NLRP3+-lymphocyte population in the MLNs increased, more pronounced in one-month-old animals. The administration of glibenclamide to pregnant rats with GD reduced the number of NLRP3+ -lymphocytes only in one-month-old offspring (by 33.0 %), whereas this index in six month-old offspring even increased.

Conclusions: Experimental prenatal hyperglycemia leads to increased proinflammatory signaling and violation of peripheral immunological tolerance formation more pronounced at one month of life.