MicroRNAs (miRNAs) have emerged as key regulators of gene expression stability implicated in cell proliferation, apoptosis, and development, whereas their altered expression has been associated with various pathological disorders. The objective of this study was to assess the expression profile of miRNAs and their predicted target genes in placentas from patients with preeclampsia (PC) and preterm (PT) labor as compared to normal term (NT) pregnancies. Using microarray profiling of 820 miRNAs and 18,630 mRNA transcripts, the analysis indicated that 283 of these miRNAs and 9119 mRNAs were expressed in all placentas, of which the relative expression of 20 miRNAs (P < .05 and ≥ 1.5-fold) and 120 mRNAs (P < .05, and 2-fold cutoff) was differentially expressed in PT and PC as compared to NT. The expression of miR-15b, miR-181a, miR-200C, miR-210, miR-296-3p, miR-377, miR-483-5p, and miR-493 and a few of their predicted target genes: matrix metalloproteinases (MMP-1, MMP-9), a disintegrin and metalloproteinase domains (ADAM-17, ADAM-30), tissue inhibitor of metalloproteinase 3 (TIMP-3); suppressor of cytokine signaling 1 (SOCS1); Stanniocalcin (STC2); corticotropin-releasing hormone (CRH), CRH-binding protein (CRHBP); and endothelin-2 (EDN2) were validated in these cohorts using real-time polymerase chain reaction (PCR), some displaying an inverse correlation with the expression of their predicted target genes. Functional analysis indicated that the products of these genes regulate cellular activities considered critical in normal placental functions and those affected by PC and PT labor. In conclusion, the results provide further evidence that placentas affected by PC and PT labor display an altered expression of a number of miRNAs with potential regulatory functions on the expression of specific target genes whose altered expression and function have been associated with these pregnancy complications.

MicroRNAs (miRNAs), through mRNA degradation or repression, act as key regulator of gene expression. Our aim was to identify specific miRNAs that are expressed in endometrium of women with and without endometriosis. We profiled the expression of 287 miRNAs in paired eutopic and ectopic endometrium and isolated endometrial cells using microarray and validated the expression of selected miRNAs using real-time PCR. On the basis of global normalization, 65 of these miRNAs were identified to be expressed above the threshold levels set during the analysis in the endometrium of women without endometriosis with a progressive decline in expression in paired eutopic and ectopic endometrium. Statistical analysis (ANOVA) identified 48 of these miRNAs as differentially expressed among these tissues and 32 miRNAs between isolated endometrial stromal cell (ESC) and glandular epithelial cell (GEC) (P < 0.05). The expression of hsa-miR20a, hsa-miR21, hsa-miR26a, hsa-miR18a, hsa-miR206, hsa-miR181a and hsa-miR142-5p, predicted to target many genes, including TGF-betaR2, ERalpha, ERbeta and PR, respectively, was validated in these tissues and cells using real-time PCR. Treatment of ESC and GEC with 17beta-estradiol and medroxyprogesterone acetate (10(-8) M) differentially regulated the expression of hsa-miR20a, hsa-miR21 and hsa-miR26a, which in part reversed following co-treatment with ICI-182780 and RU-486 (10(-6) M), respectively (P < 0.05). In conclusion, we provided evidence for the expression of a number of differentially expressed miRNAs in eutopic/ectopic endometrium and isolated endometrial cells, opening up the possibility that aberrant/altered expression of some miRNAs whose expression is regulated by the ovarian steroids may influence the expression of specific target genes with central roles in normal endometrial cellular activities and pathogenesis of endometriosis.

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MicroRNAs (miRNAs) which regulate gene expression stability displayed an aberrant expression profile in ectopic endometrium (ECE) as compared to eutopic (EUE) and normal endometrium (NE). We assessed the expression of miR-17-5p, miR-23a, miR-23b and miR-542-3p, their predicted target genes, steroidogenic acute regulatory protein, aromatase and cyclooxygenase-2, and influence of ovarian steroids on their expression in endometrial stromal (ESC) and glandular epithelial cells (GEC). The results indicated a lower expression of miR-23b and miR-542-3p and higher level of miR-17-5p in paired ECE and EUE as compared with NE. These levels were elevated and inversely correlated with the level of expression of their respective target genes in ECE. The expression of these miRNAs and genes was differentially regulated by 17β-estradiol, medroxyprogesterone acetate, ICI-182780 and RU-486, or their respective combinations in ESC and GEC. We concluded that altered expression of specific miRNAs in ECE, affecting the stability of their target genes expression, has direct implications in pathogenesis of endometriosis.

WJ. Effect of maternal undernutrition on vascular expression of micro and messenger RNA in newborn and aging offspring. Am J Physiol Regul Integr Comp Physiol 298: R1366 -R1374, 2010. First published March 3, 2010 doi:10.1152/ajpregu.00704.2009.-The aim of this study was to test the hypothesis that maternal undernutrition (MUN) alters offspring vascular expression of micro-RNAs (miRNAs), which, in turn, could regulate the expression of a host of genes involved with angiogenesis and extracellular matrix remodeling. The expression of miRNA and mRNA in the same aortic specimens in 1-day-old (P1) and 12-mo-old offspring aortas of dams, which had 50% food restriction from gestation day 10 to term, was determined by specific rat miRNA and DNA arrays. MUN significantly downregulated the expression of miRNAs 29c, 183, and 422b in the P1 group and 200a, 129, 215, and 200b in the 12-mo group, and upregulated the expression of miRNA 189 in the P1 group and 337 in the 12-mo group. The predicted target genes of the miRNAs altered in the two age groups fell into the categories of: 1) structural genes, such as collagen, elastin, and enzymes involved in ECM remodeling; and 2) angiogenic factors. MUN primarily altered the expression of mRNAs in the functional category of cell cycle/mitosis in the P1 group and anatomic structure and apoptosis in the 12-mo age group. Several of the predicted target genes of miRNAs altered in response to MUN were identified by the DNA array including integrin-␤ 1 in the P1 aortas and stearoyl-CoA desaturase-1 in the 12-mo age groups. These results are consistent with the hypothesis that MUN modulation of offspring gene expression may be mediated in part by a miRNA mechanism. aorta; DNA array MICRO-RNAs (miRNAs) are short, noncoding RNA molecules of 20 -25 nucleotides in length that regulate gene expression at the posttranscriptional level (2, 4) and play a significant role in the regulation of physiologic and pathologic processes. Several thousand miRNAs have been cloned and/or predicted and may regulate up to 90% of human protein-coding genes, primarily through translational repression, and, in some cases, mRNA degradation (9,19,35). The role of miRNAs in fetal development and postnatal maturation is largely unstudied, and their role in fetal programming of adult disease is unknown. It is well known that maternal undernutrition (MUN) alters fetal gene expression, and changes in transcription rates cannot explain all these effects. Therefore, we have hypothesized that MUN influences the expression of offspring miRNAs, which then would influence processing of key developmental proteins, and this might represent a novel epigenetic mechanism for regulation of gene expression in the offspring.Previously, we reported that MUN induced significant vascular remodeling of offspring vascular extracellular matrix (17, 18) and inhibited angiogenesis (16). miRNAs have been shown to play a role in the regulation of both of these processes, and therefore we sought to determine whether MUN alters miRNA express...