Methylation of Promoter Regions of Genes of the Human Intrauterine Renin Angiotensin System and Their Expression

[摘要] The intrauterine renin angiotensin system (RAS) is implicated in placentation and labour onset. Here we investigate whether promoter methylation of RAS genes changes with gestation or labour and if it affects gene expression. Early gestation amnion and placenta were studied, as were term amnion, decidua, and placenta collected before labour (at elective caesarean section) or after spontaneous labour and delivery. The expression and degree of methylation of the prorenin receptor (ATP6AP2), angiotensin converting enzyme (ACE), angiotensin II type 1 receptor (AGTR1), and two proteases that can activate prorenin (kallikrein,KLK1, and cathepsin D,CTSD) were measured by qPCR and a DNA methylation array. There was no effect of gestation or labour on the methylation of RAS genes andCTSD. Amnion and decidua displayed strong correlations between the percent hypermethylation of RAS genes andCTSD, suggestive of global methylation. There were no correlations between the degree of methylation and mRNA abundance of any genes studied.KLK1was the most methylated gene and the proportion of hypermethylatedKLK1alleles was lower in placenta than decidua. The presence of intermediate methylated alleles ofKLK1in early gestation placenta and in amnion after labour suggests thatKLK1methylation is uniquely dynamic in these tissues.

[学科分类] 内分泌与代谢学