The online version of this article (doi:10.1186/1477-7827-10-1) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
MS contributed to designing the study, acquisition of data, analysis and interpretation of data, and in writing the manuscript. PW participated in the in the acquisition and interpretation of the data. As Principal Investigators, JS and JPP were involved in the intellectual and experimental programming of the study, the assays and interpretation of data, and writing the manuscript. All authors read and approved the final manuscript.
A decrease in HOXA11 expression in eutopic mid-secretory endometrium has been found in women with endometriosis-associated infertility.
Using Real-time quantitative PCR (RQ-PCR) and western blotting analysis we studied the HOXA11 transcript and protein levels in mid-luteal eutopic endometrium from eighteen infertile women with minimal endometriosis, sixteen healthy fertile women and sixteen infertile women with fallopian tubal occlusion from the Polish population. We also evaluated transcript levels of DNA methyltransferases DNMT1, DNMT3A and DNMT3B in these groups of women.
There were significantly lower levels of HOXA11 transcripts (p = 0.003, p = 0.041) and protein (p = 0.004, p = 0.001) in women with endometriosis as compared to fertile women and infertile women with tubal occlusion. Moreover, we found significantly higher methylation levels of the CpG region in the first exon of HOXA11 in infertile women with endometriosis compared with fertile women (p < 0.001) and infertile women with tubal occlusion (p < 0.001). We also observed significantly increased levels of DNMT3A transcript in women with endometriosis than fertile women (p = 0.044) and infertile women with tubal occlusion (p = 0.047). However, we did not observe significant differences in DNMT1 and DNMT3B transcript levels between these investigated groups of women.
We confirmed that reduced HOXA11 expression may contribute to endometriosis-associated infertility. Moreover, we found that DNA hypermethylation can be one of the possible molecular mechanisms causing a decrease in HOXA11 expression in the eutopic mid-secretory endometrium in infertile women with endometriosis.
Additional file 1: Supplemental Table S1. Primer sequences used for RQ-PCR analysis and bisulfite sequencing of HOXA11 regions I, II, and III. (PDF 14 KB)12958_2011_937_MOESM1_ESM.PDF
Additional file 2: Supplemental Figure S1. Location of CpG-rich regions I, II, and III in the human HOXA11 gene. (PDF 66 KB)12958_2011_937_MOESM2_ESM.PDF
Authors’ original file for figure 112958_2011_937_MOESM3_ESM.pdf
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Ulukus M, Cakmak H, Arici A: The role of endometrium in endometriosis. J Soc Gynecol Investig. 2006, 13: 467-476. PubMed
Houston DE: Evidence for the risk of pelvic endometriosis by age, race and socioeconomic status. Epidemiol Rev. 1984, 6: 167-191. PubMed
Strathy JH, Molgaard CA, Coulam CB, Melton LJ: Endometriosis and infertility: a laparoscopic study of endometriosis among fertile and infertile women. Fertil Steril. 1982, 38: 667-672. PubMed
Simón C, Gutiérrez A, Vidal A, de los Santos MJ, Tarín JJ, Remohí J, Pellicer A: Outcome of patients with endometriosis in assisted reproduction: results from in vitro fertilization and oocyte donation. Hum Reprod. 1994, 9: 725-729. PubMed
Tummon IS, Maclin VM, Radwanska E, Binor Z, Dmowski WP: Occult ovulatory dysfunction in women with minimal endometriosis or unexplained infertility. Fertil Steril. 1988, 50: 716-720. PubMed
Kao LC, Germeyer A, Tulac S, Lobo S, Yang JP, Taylor RN, Osteen K, Lessey BA, Giudice LC: Expression profiling of endometrium from women with endometriosis reveals candidate genes for disease-based implantation failure and infertility. Endocrinology. 2003, 144: 2870-28781. 10.1210/en.2003-0043. CrossRefPubMed
Canis M, Donnez JG, Guzick DS, Halme JK, Rock JA, Schenken RS, et al: Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997, 67: 817-821. 10.1016/S0015-0282(97)81391-X. CrossRef
Tvarijonaviciene E, Nadisauskiene RJ: The value of hysterosalpingography in the diagnosis of tubal pathology among infertile patients. Medicina. 2008, 44: 439-448. PubMed
Noyes RW, Hertig AT, Rock J: Dating the endometrial biopsy. Fertil Steril. 1950, 1: 3-5.
CPG Plot Search for Regions of Genomic Sequences that are Rich in the CpG pattern. [ http://www.ebi.ac.uk/emboss/cpgplot/]
TESS: Transcription Element Search System. [ http://www.cbil.upenn.edu/cgi-bin/tess/tess]
BiQ Analyzer - a software tool for DNA methylation analysis. [ http://biq-analyzer.bioinf.mpi-sb.mpg.de/]
BDPC DNA methylation analysis platform. [ http://biochem.jacobs-university.de/BDPC/Compilation/manual.php]
SYSTAT/Statistical and Graphical Software. [ http://www.systat.com/]
Hsieh-Li HM, Witte DP, Weinstein M, Branford W, Li H, Small K, Potter SS: Hoxa 11 structure, extensive antisense transcription, and function in male and female fertility. Development. 1995, 121: 1373-1385. PubMed
Benson GV, Lim H, Paria BC, Satokata I, Dey SK, Maas RL: Mechanisms of reduced fertility in Hoxa-10 mutant mice: uterine homeosis and loss of maternal Hoxa-10 expression. Development. 1996, 122: 2687-2696. PubMed
Taylor HS, Igarashi P, Olive DL, Arici A: Sex steroids mediate HOXA11 expression in the human peri-implantation endometrium. J Clin Endocrinol Metab. 1999, 84: 1129-1135. 10.1210/jc.84.3.1129. PubMed
Rackow BW, Jorgensen E, Taylor HS: Endometrial polyps affect uterine receptivity. Fertil Steril. 2011, doi:10.1016/j.fertnstert.2010.12.034
Turek-Plewa J, Jagodziński PP: The role of mammalian DNA methyltransferases in the regulation of gene expression. Cell Mol Biol Lett. 2005, 10: 631-647. PubMed
- Expression of HOXA11 in the mid-luteal endometrium from women with endometriosis-associated infertility
Paweł P Jagodziński
- BioMed Central
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