Abstract 152: Downregulation of Placental Genes are Associated With the Development of Maternal Syndrome in Dahl Salt-Sensitive Rats

Abstract

The Dahl Salt-Sensitive rat maintained on a low salt, casein-based diet (SSC) develops maternal syndrome (hypertension and proteinuria) compared to virgin controls. Our group has previously demonstrated that a substitution of the casein protein for a wheat gluten protein in the rat chow (SSWG) protects the Dahl SS rat from the development of maternal syndrome. This protection is observed in both the blood pressure (141±3 vs 114±4 mmHg, p <0.001, SSC vs. SSWG, respectively) and proteinuria (98±16 vs 52±12 mg/day, p <0.01). It is also associated with an improvement in uterine artery resistance index (0.9±0.02 vs 0.5±0.04, p< 0.01) suggesting dietary protein source influences pregnancy in Dahl SS rats. While the exact mechanisms responsible for the development of maternal syndrome are unclear, it is thought that poor placentation is the initiating step in the disease process. Since a substitution of the protein source in the rat chow greatly impacted the phenotype in the Dahl SS rat, we tested the hypothesis that there was differential gene expression in the placental tissue between the SSC rats prone to maternal syndrome compared to the protected SSWG rats. To investigate these phenotypic differences, a PCR array approach was utilized to explore gene expression in placental tissue of both SSC and SSWG rats. Placental tissue from both strains at gestational day 20 was homogenized and RNA isolated to investigate 89 genes related to rat pregnancy and preeclampsia. Using a commercially available PCR array approach identified 4 genes that were differentially expressed between the SSC and SSWG placentas. There was a significant downregulation in expression of Atp1b1 (0.0018-fold change, p <0.01) , Nos3 (0.13-fold change, p <0.005) , Cdh13 (0.42-fold change, p <0.05) and Cyp26a1 (0.48-fold change, p <0.05) in the SSC compared to the SSWG rats. All four of these genes have been demonstrated to play roles in the placentation phase of gestation in other animal models. These results suggest that downregulation of these genes in placentas of the SSC rats, as a result of alterations in dietary protein intake, contributes to the maternal syndrome phenotype and provide avenues for future studies.