Systemic inflammation in pregnant obese women is associated with 1.5- to 2-fold increase in serum Interleukin-6 (IL-6) and newborns with lower kidney/body weight ratio but the role of IL-6 in increased susceptibility to chronic kidney (CKD) in adult progeny is not known. Since IL-6 crosses the placental barrier, we administered recombinant IL-6 (10 pg/g) to pregnant mice starting at mid-gestation yielded newborns with lower body (p < 0.001) and kidney (p < 0.001) weights. Histomorphometry indicated decreased nephrogenic zone width (p = 0.039) with increased numbers of mature glomeruli (p = 0.002) and pre-tubular aggregates (p = 0.041). Accelerated maturation in IL-6 newborns was suggested by early expression of podocyte-specific protein podocin in glomeruli, increased 5-methyl-cytosine (LC-MS analysis for CpG DNA methylation) and altered expression of certain genes of cell-cycle and apoptosis (RT-qPCR array-analysis). Western blotting showed upregulated pJAK2/pSTAT3. Thus, treating dams with IL-6 as a surrogate provides newborns to study effects of maternal systemic inflammation on future susceptibility to CKD in adulthood.
Srivastava, T., Joshi, T., Heruth, D. P., Rezaiekhaligh, M., Garola, R. E., Zhou, J., Boinpelly, V. C., Ali, M., Alon, U. S., Sharma, M., Vanden Heuvel, G. B., Mahajan, P., Priya, L., Jiang, Y., McCarthy, E. T., Savin, V. J., Sharma, R., Sharma, M. A mouse model of prenatal exposure to Interleukin-6 to study the developmental origin of health and disease. Sci Rep 11, 13260-13260 (2021).