Renal Transcriptome Analysis of Programmed Hypertension Induced by Maternal Nutritional Insults

Int J Mol Sci. 2015 Aug 3;16(8):17826-37. doi: 10.3390/ijms160817826.

Abstract

Maternal nutrition can affect development, leading to long-term effects on the health of offspring. The most common outcome is programmed hypertension. We examined whether alterations in renal transcriptome are responsible for generating programmed hypertension among four different models using next-generation RNA sequencing (NGS) technology. Pregnant Sprague-Dawley rats received 50% caloric restriction (CR), intraperitoneal injection of 45 mg/kg streptozotocin, 60% high-fructose (HF) diet, or 1% NaCl in drinking water to conduct CR, diabetes, HF, or high-salt models, respectively. All four models induced programmed hypertension in adult male offspring. We observed 16 shared genes in a two-week-old kidney among four different models. The identified differential expressed genes (DEGs) that are related to the regulation of blood pressure included Adrb3, Alb, Apoe, Calca, Kng1, Adm2, Guca2b, Hba2, Hba-a2, and Ppara. The peroxisome proliferator-activated receptor (PPAR) signaling pathway and glutathione metabolism pathway were shared by the CR, diabetes, and HF models. Conclusively, a variety of maternal nutritional insults induced the same phenotype-programmed hypertension with differential alterations of renal transcriptome in adult male offspring. The roles of DEGs identified by the NGS in this study deserve further clarification to develop ideal maternal dietary interventions and thus spare the next generations from the burden of hypertension.

Keywords: developmental programming; diabetes; fructose; hypertension; next generation sequencing; nutrition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caloric Restriction
  • Dietary Carbohydrates / adverse effects
  • Female
  • Fructose / toxicity
  • Glutathione / metabolism
  • Hypertension / etiology*
  • Hypertension / genetics
  • Hypertension / metabolism
  • Kidney / metabolism*
  • Male
  • Maternal Nutritional Physiological Phenomena*
  • Peroxisome Proliferator-Activated Receptors / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Chloride, Dietary / adverse effects
  • Streptozocin / toxicity
  • Transcriptome*

Substances

  • Dietary Carbohydrates
  • Peroxisome Proliferator-Activated Receptors
  • Sodium Chloride, Dietary
  • Fructose
  • Streptozocin
  • Glutathione