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

妊娠期营养失衡是子代高血压的危险因素。本研究以自发性高血压卒中易感（spontaneously hypertensive stroke-prone, SHRSP）大鼠为模型，发现妊娠期母体蛋白质限制可调控肾脏前列腺素E受体1（prostaglandin E receptor 1, Ptger1）的DNA甲基化状态，并显著上调其表达，该受体的表达变化与子代高血压的发生密切相关。肾脏Ptger1的DNA甲基化特征表现为基因内CpG岛高度甲基化，而启动子区域则呈现低甲基化趋势。进一步研究显示，胎儿期Ptger1 DNA甲基化的改变在出生后得以保留并增强，有力佐证了这一表观遗传标记的稳定保守性。然而，断奶后采用高、低蛋白质饮食干预，均可改善胎儿营养不良引发的Ptger1 DNA高甲基化，提示产后营养环境干预可改变并重编程表观遗传修饰。本研究结果为高血压预防及前瞻性治疗策略提供了新的研究视角。
整体实验设计：选取胎儿期暴露于低蛋白质饮食的子代大鼠，于出生后第28天采集肾脏组织进行DNA提取及亚硫酸氢盐测序（bisulfite sequencing）。我们通过整合甲基化组（methylome）与转录组（transcriptome）测序分析数据，筛选候选基因。