Alteration and Reprogramming of Renal Ptger1 DNA Methylation Induced by Maternal Protein Restriction in SHRSP Offspring

Nutrient imbalances during gestation are a risk factor for hypertension in offspring. In this study, we found that, in spontaneously hypertensive stroke-prone (SHRSP) rats, maternal protein restriction during gestation modulates the DNA methylation status and significantly upregulates the expression of renal prostaglandin E receptor 1 (Ptger1), which is associated with hypertension in offspring. Renal Ptger1 DNA methylation is characterized by hypermethylation of CpG islands within the gene and a tendency toward hypomethylation in promoter regions. Furthermore, we observed that changes in fetal Ptger1 DNA methylation status after birth were preserved and enhanced, strongly supporting the stable conservation of this epigenetic marker. However, post-weaning low- or high-protein diets ameliorated Ptger1 DNA hypermethylation caused by fetal malnutrition, indicating postnatal nutritional environment interventions can alter and reprogram epigenetic modifications. These findings provide new insights into hypertension prevention and prospective therapeutic strategies. Overall design: Kidneys of offspring exposed to a low-protein diet during fetal life were selected at postnatal day 28 for DNA extraction and bisulfite sequencing. we searched for candidate genes by integrating data from both methylome and transcriptome profiling.