Mol. Hum. Reprod. Advance Access published online on August 31, 2007
Molecular Human Reproduction, doi:10.1093/molehr/gam063
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The Expression Profile of Micro-RNA In Endometrium and Endometriosis and the Influence of Ovarian Steroids on their Expression
Department of OB/GYN University of Florida, Gainesville, Fl 32610
1 Address Correspondence: Dr. Nasser Chegini Department of OB/GYN, University of Florida, Box 100294, Gainesville FL. 32610, Tel: (352) 392-3929, Fax: (352) 392-6994, E.Mail: cheginin{at}obgyn.ufl.edu
Abstract: 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 realtime PCR. Based on 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 (ESC) and glandular epithelial (GEC) cells (P<0.05). The expression of hsa-miR20a, hsa-miR21, hsa-miR26a, hsa-miR18a, hsa-miR206, hsa-miR181a, and hsa-miR142-5p, predicated to target many genes, including TGF-ßR2, ER
, ERß and PR, respectively was validated in these tissues and cells using realtime PCR. Treatment of ESC and GEC with 17ß estradiol and medroxyprogesterone acetate (10–8 M) differentially regulated the expression of hsa-miR20a, hsa-miR21, 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.
Key Words: endometrium/endometriosis/miRNA/expression/regulation
Submitted on July 27, 2007; accepted on August 21, 2007.
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