Maternal Protein Restriction Alters the Renal Ptger1 DNA Methylation State in SHRSP Offspring.

Moe Miyoshi,Masayuki Sato,Kenji Saito,Fumihito Miura,Huijuan Jia,Katsuhiko Shirahige,Hisanori Kato,Lila Otani,Takashi Ito

doi:10.3390/nu10101436

Abstract

We previously reported that maternal protein restriction (LP) during pregnancy increases salt sensitivity in offspring using the Stroke-Prone Spontaneously Hypertensive Rat (SHRSP). In the present study, we focus on DNA methylation profiles of prostaglandin E receptor 1 gene (ptger1), which is known to be associated with hypertension. We evaluated the ptger1 DNA methylation status via bisulfite sequencing, and analyzed the expression of ptger1-related genes. The results of these analyses showed that, compared to controls, the LP-S offspring exhibited both marked ptger1 hypermethylation, and significantly increased ptger1 expression. Moreover, they also exhibited significantly decreased expression of the downstream gene epithelial Na+ channel alpha (enacα). Interestingly, LP offspring that were provided with a standard water drinking supply (W) also exhibited increased ptger1 methylation and expression. Together, these results suggest that maternal protein restriction during pregnancy modulates the renal ptger1 DNA methylation state in SHRSP offspring, and thereby likely mediates ptger1 and enacα gene expression to induce salt sensitivity.

Highlights

In recent years, the concept that the fetal nutritional state affects the lifetime risk of pathophysiological processes associated with chronic diseases, (i.e., the ‘Fetal Origins of Adult Disease (FOAD)’, and ‘Developmental Origins of Health and Disease (DOHaD)’ concepts originally proposed by Barker in the 1990s [1,2,3]), has become widely accepted
No significant differences were observed between the liquid consumption of the CN-W and significant wereLP-S
No significant difference in urinary volume was observed between the CN-W and LP-W, nor the

Summary

Introduction

The concept that the fetal nutritional state affects the lifetime risk of pathophysiological processes associated with chronic (including especially non-communicable) diseases, (i.e., the ‘Fetal Origins of Adult Disease (FOAD)’, and ‘Developmental Origins of Health and Disease (DOHaD)’ concepts originally proposed by Barker in the 1990s [1,2,3]), has become widely accepted. Previous studies have shown that DNA methylation changes tend to be retained in chromatin across generations [8]; they have been proposed as possible key mechanisms that underlie DOHaD [9,10,11]. The Stroke-Prone Spontaneously Hypertensive rat (SHRSP) naturally develops stroke as a result of harboring a heredity factor that causes hypertension, and has been widely used as a research model for cardiovascular diseases.

Methods

Discussion

Conclusion