Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA252

Poster Communications

The effect of prenatal dexamethasone exposure on renal expression of glucose transporters in rat fetuses and offspring

S. A. Malatiali1, M. Al-Awadi1, M. Al-Bader1

1. Department of Physiology, Faculty of Medicine, Kuwait University, Kuwait, Kuwait.

Introduction: Dexamethasone (Dex), a synthetic glucocorticoid (GC), is administered to pregnant mothers at risk of preterm delivery, to induce fetal lung maturation. Offspring exposed to maternal GCs show altered glucose homeostasis such as fasting hyperglycemia, increased hepatic and renal gluconeogenesis, decreased pancreatic β cell number, hyperinsulinemia and decreased glucose tolerance, all of which increase the risk of diabetes development. We hypothesized that the impaired glucose homeostasis can be further exacerbated by the increase in renal proximal glucose reabsorption through the upregulation of sodium-glucose transporters (SGLTs) and glucose transporters (GLUTs), as seen in diabetic patients and animals. Therefore, the aim of this study was to investigate the effect of maternal treatment with Dex on fetal and postnatal renal expression of SGLTs and GLUTs. Methods: Pregnant Sprague Dawley dams were randomly divided into 2 groups: saline-treated controls (n: number of dams=6/group) and Dex-treated with 0.2 mg/kg i.p. from day 15 of pregnancy till 21 days gestation (dg). Gene expression of SGLT1, SGLT2, GLUT1 and GLUT2 was studied in the kidneys of fetuses at 19 and 21 dg and in 1-month and 4-month-old male and female offspring using real-time PCR. For body and kidney weights, results are expressed as mean ± SEM and comparisons were performed using unpaired t-test. For PCR, amplification efficiencies and quantitation cycle (Cq) were derived from the raw data using LinReg software. Calculation of fold change and significance were done using REST software. Results: Maternal treatment with Dex caused decreases in body weights of fetuses at 21 dg (4.56 ± 0.12 g vs. 5.58 ± 0.16 9 g, p<0.001). Dex did not affect body or kidney weights of female adult rats, however at 4 months, males had lower body weights (473.8 ± 9.7 vs. 521.6 ± 11.4, p < 0.01) and kidney weight/body weight (0.003 ± 0.0002 vs. 0.0024 ± 0.0001, p<0.05) when compared to controls. Dex treatment had no effect on SGLTs expression in male offspring at any stage, however, in 19 dg females SGLT1 mRNA was increased by 1.78 folds (p<0.05) and in 21 dg females GLUT2 mRNA was increased by 3.59 folds (p<0.001). Conclusions: Maternal Dex treatment causes intrauterine growth restriction towards the end of gestation. Despite the decrease in male body and kidney weights, the effect of Dex on glucose transporters' gene expression was only seen in female fetuses. This effect is therefore, not attributed to growth restriction, but rather due to a direct effect of Dex on renal tubules that express GCs receptors. Membrane expression of SGLTs and GLUTs in this model will provide a better understanding of the role of Dex in prenatal programming.

Where applicable, experiments conform with Society ethical requirements