Experimental gestational diabetes disrupts the formation of immune tolerance in offspring

Abstract

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 polymerase 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 transcriptional 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.