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

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

FOXO transcription factors : from cell fate decisions to regulation of human female reproduction

All key reproductive events in the human ovary and uterus, including follicle activation, ovulation, implantation, decidualization, luteolysis and menstruation, are dependent upon profound tissue remodelling, characterised by cyclical waves of cell proliferation, differentiation, apoptosis, tissue breakdown and regeneration. FOXO transcription factors, an evolutionarily conserved subfamily of the forkhead transcription factors, have emerged as master regulators ofcell fate decision capable ofintegrating avariety ofstress, growth factor and cytokine signaling pathways with the transcription machinery. The ability of FOXOs to regulate seemingly opposing cellular responses, ranging from cell cycle arrest and oxidative stress responses to differentiation and apoptosis, renders these transcription factors indispensable for cyclic tissue remodelling in female reproduction. Conversely, perturbations in the expression or activity of FOXO transcription factors are increasingly linked to common reproductive disorders, such as pregnancy loss, endometriosis, endometrial cancer and primary ovarian insufficiency