S-43-3: INTRAUTERINE GROWTH RESTRICTION CAUSES AN ALTERATION IN KIDNEY GENE EXPRESSION

Abstract

High blood pressure (BP) and kidney disease are the leading cause of death in the world population. Experimental and epidemiological studies indicate that the fetal environment is critical in determining adult cardiovascular (CV)-renal outcome. It is known that intrauterine growth restriction (IUGR) or low birth weight (LBW) induces an increased risk of hypertension and kidney disease in later life. Placental insufficiency is the common cause of IUGR. Low birth weight is a significant public health problem globally and is associated with short- and long-term consequences. About 15–20% of all births worldwide are LBW, representing more than 20 million births a year. Clinical studies indicate that birth weight is positively associated with glomerular filtration rate (GFR) and negatively associated with BP. Also, animal models of IUGR exhibit a higher susceptibility to ANGII induced high BP and kidney damage in response to acute ischemic reperfusion injury. Thus, these data suggest that IUGR programs greater risk of hypertension and renal dysfunction. However, the exact mechanisms linking an adverse fetal environment with a later increased risk of these diseases are unclear. Objective: This study aims to evaluate the global genetic change in the kidney of the animal model of IUGR. Design: female C57Bl/6J were mated with male C57bl/6J. Upon confirming the pregnancy by sperm plug (day 0 of gestation), the pregnant animal will be undergone reduced uterine perfusion surgery (RUP) or shame surgery at day 13 of gestation. The offspring of RUP mom will be labeled as IUGR, and from the sham will be labeled as control. The offspring will be used for blood pressure measurement using radio-telemetry and kidney microarray analysis when they reach 24 weeks. Results: Th IUGR offspring significantly has an increase in blood pressure compared to the control. The kidneys of male IUGR have 6529 gene upregulation compared to male control. The make IUGR also has 5713 genes dow-regulation as compared to same-sex control. The female IUGR has 1635 genes upregulated and 1513 genes downregulated compared to the kidney from the female control group. Conclusion: the complication during pregnancy, such as reduced uterine perfusion, which is commonly found in preeclampsia programs, alters gene expression in the kidneys of their offspring. This finding suggests that IUGR causes the gene alteration in the kidneys, which is the primary organ in controlling the blood pressure of the offspring, and may lead to the development of hypertension and kidney disease.