MicroRNA expression profiling of eutopic secretory endometrium in women with versus without endometriosis

Abstract

Endometriosis is a common gynecologic disorder characterized by pain and infertility. In addition to estrogen dependence, progesterone resistance is an emerging feature of this disorder. Specifically, a delayed transition from the proliferative to secretory phase as evidenced by dysregulation of progesterone target genes and maintenance of a proliferative molecular fingerprint in the early secretory endometrium (ESE) has been reported. MicroRNAs (miRNAs) are small noncoding RNAs that collectively represent a novel class of regulators of gene expression. In an effort to investigate further the observed progesterone resistance in the ESE of women with endometriosis, we conducted array-based, global miRNA profiling. We report distinct miRNA expression profiles in the ESE of women with versus without endometriosis in a subset of samples previously used in global gene expression analysis. Specifically, the miR-9 and miR-34 miRNA families evidenced dysregulation. Integration of the miRNA and gene expression profiles provides unique insights into the molecular basis of this enigmatic disorder and, possibly, the regulation of the proliferative phenotype during the early secretory phase of the menstrual cycle in affected women.

Figure 1

Unsupervised hierarchial clustering of differentially expressed miRNAs in ESE from women with versus without endometriosis (fold change of ≥1.5).

Figure 2

Validation by qRT–PCR analysis of miRNA expression. Data are presented as fold change of expression in eutopic endometrium from women with endometriosis relative to expression in endometrium from women without endometriosis after normalization to miR-5S. For comparative analysis, the expression values for each miRNA were set as 1 in ESE from women without endometriosis. Significant fold changes are marked by *P = 0.05; **P < 0.05. Data are mean ± SEM.