P 55 Role of uric acid and GLUT9 in pregnancy on neonatal development

Abstract

Introduction High maternal uric acid serum levels are often associated with preeclampsia. The regulation of the placental uric acid transport system and its major uric acid transporter, glucose transporter 9 (GLUT9) are not fully understood yet. We hypothesized that the lack of GLUT9 in the placenta leads to exposure of high uric acid levels in the fetus. Objectives Using a systemic GLUT9 knockout mice model we aim to understand the effect of fetal hyperuricemia on the growth of the pups and the development of their internal organs. Methods Six-week-old female GLUT9(+/−) mice, maintained on regular chow diet, are mated with GLUT9(+/−) male mice. After the mating the diet is changed to regular chow diet plus inosine for the entire pregnancy period (21 days), which will lead to hyperuricemia in GLUT9(-/-) fetal mice, but not in the maternal mice. Starting from day 7 after birth the pups are daily weighted until day 70 after birth. At day 70 the pups are sacrificed and after perfusion organs (pancreas, liver and kidney) are weighted and used for tissue analysis to identify possible abnormal organ development. Results Neonatal GLUT9(−/−) mice were smaller than GLUT9(+/+) mice. Significant differences in body weight between neonatal GLUT9(+/+) and GLUT9(−/−) were observed in female mice from day 12 until day 35 and in male mice from day 18 till day 21 and 39 until day 48. Then when we compared kidneys from neonatal GLUT9(+/+) and GLUT9(−/−) female mice, we saw a decreased in size of 25 ± 0.15% ( n = 7; p = 0.007, Student’s T -test) in the left kidney and of 35 ± 0.21% ( n = 7; p = 0.011) in the right one. Hematoxylin & eosin staining on kidney paraffin sections shows that the morphology of the kidney of GLUT9(+/+) mice is normal with normal kidney tubules with viable epithelial cells; while the morphology of the kidney of GLUT9(−/−) mice is typical of necrotic tissue. These kidneys are characterised by necrosis of epithelial cells, with loss of nuclei, fragmentation of cells, and leakage of contents. Conclusion Hyperuricemia may cause the impaired development of neonatal GLUT9(−/−) mice. The understanding of the mechanism behind might underlie the possible link between hyperuricemia and altered placental function which may affect neonatal growth pattern.