Effect of Gestational Diabetes in Female Rats on Brain Astrocyte Functions in Their Offspring

Gestational diabetes mellitus (GDM) in the mother may impair fetal brain development through epigenetic mechanisms and metabolic dysregulation of glial cells. The present study aims to investigate functional changes in astrocytes derived from the brains of neonatal rats born to females with streptozotocin-induced GDM. It was found that maternal GDM not only led to hypoglycemia in newborn pups but also increased the proliferation of primary cortical astrocytes under glucose deprivation compared to control. Astrocyte proliferation in response to activation of protease-activated receptor 1 (PAR1) by a peptide agonist did not differ in the GDM and control groups. Astrocyte proliferation was increased in glucose-containing medium, while glucose deprivation either had no effect or suppressed proliferation. Interestingly, noticeable lipopolysaccharide (LPS)-induced activation of primary astrocytes observed in the control group was completely abolished in the GDM group, as indicated by IL-6 secretion levels. These findings suggest that intrauterine exposure to GDM may program long-term alterations in the metabolic and immune activity of fetal astrocytes.