Volume 6, Issue 1 (Spring 2018 2018)                   Jorjani Biomed J 2018, 6(1): 1-11 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Larki S, Maleki M. DNA hypomethylation of the nuclear receptor subfamily 5 (NR5A1) gene promoter is associated with endometriosis among women in north west of Iran. Jorjani Biomed J. 2018; 6 (1) :1-11
URL: http://goums.ac.ir/jorjanijournal/article-1-587-en.html
1- MSc of Genetic, Department of Biology, Islamic Azad University, Tabriz Branch, Tabriz, Iran
2- Assistant Professor, Department of Biology, Islamic Azad University, Tabriz Branch, Tabriz, Iran , maleki.masuod@gmail.com
Abstract:   (916 Views)
Background and objectives: Endometrial tissue growth and its activity outside the uterus cause endometriosis. It has been suggested that various epigenetic deviations play a major role in the pathogenesis of endometriosis. Steroidogenic factor 1 (SF-1; NR5A1) is an essential transcription factor for estrogen biosynthesis in endometrial cells. The expression of SF-1 in endometriosis and lack of expression in normal endometrium is primarily determined by its promoter methylation. Here, we aimed to compare the methylation status of the SF-1 gene promoter region in women with endometriosis in comparison to healthy subjects.
Methods: In the present case–control study, DNA was extracted from 25 endometrial tissue samples from women with endometriosis and 5 normal post-hysterectomy endometrium tissues which were collected from Tabriz hospitals including Vali-e-Asr, Taleghani, 29 Bahman and Shams in 2016. The obtained DNA samples were subjected to Bisulfite-treatment. Finally, the status of SF-1gene promoter methylation was evaluated by methylation specific PCR method. Statistical analyses including descriptive and inferential statistics were conducted using tables, bar charts by statistical software SPSS version 20 and independence test.
Results: The methylation status of SF-1 gene promoter was decreased significantly in endometriosis samples (P<0.05).  
Conclusion: SF-1 gene promoter hypomethylation could increase the relative expression of SF-1 gene in endometriosis which may lead to the development or progression of the disease.
Full-Text [PDF 287 kb]   (357 Downloads)    
Type of Article: Original article | Subject: Molecular Sciences
Received: 2018/08/19 | Revised: 2019/08/5 | Accepted: 2018/08/19

1. Giudice LC, Kao LC. Endometriosis. Lancet (London, England). 2004 Nov 13-19;364(9447):1789-99. PubMed PMID: 15541453. Epub 2004/11/16. eng. [DOI:10.1016/S0140-6736(04)17403-5]
2. Guo SW. Emerging drugs for endometriosis. Expert opinion on emerging drugs. 2008 Dec;13(4):547-71. PubMed PMID: 19046127. Epub 2008/12/03. eng. [DOI:10.1517/14728210802548360]
3. Vercellini P, Pietropaolo G, De Giorgi O, Pasin R, Chiodini A, Crosignani PG. Treatment of symptomatic rectovaginal endometriosis with an estrogen-progestogen combination versus low-dose norethindrone acetate. Fertility and sterility. 2005;84(5):1375-87. [DOI:10.1016/j.fertnstert.2005.03.083]
4. Rock JA, Zacur HA, Dlugi AM, JONES Jr HW, TeLINDE RW. Pregnancy success following surgical correction of imperforate hymen and complete transverse vaginal septum. Obstetrics & Gynecology. 1982;59(4):448-51.
5. Missmer SA, Hankinson SE, Spiegelman D, Barbieri RL, Michels KB, Hunter DJ. In utero exposures and the incidence of endometriosis. Fertility and sterility. 2004;82(6):1501-8. [DOI:10.1016/j.fertnstert.2004.04.065]
6. Guzick DS, Silliman NP, Adamson GD, Buttram VC, Canis M, Malinak LR, et al. Prediction of pregnancy in infertile women based on the American Society for Reproductive Medicine's revised classification of endometriosis. Fertility and sterility. 1997;67(5):822-9. [DOI:10.1016/S0015-0282(97)81392-1]
7. Kettel LM, Murphy AA, Morales AJ, Ulmann A, Baulieu EE, Yen SS. Treatment of endometriosis with the antiprogesterone mifepristone (RU486). Fertility and sterility. 1996;65(1):23-8. [DOI:10.1016/S0015-0282(16)58022-4]
8. Hayes EC, Rock JA. COX-2 inhibitors and their role in gynecology. Obstetrical & gynecological survey. 2002;57(11):768-80. [DOI:10.1097/00006254-200211000-00023]
9. Vercellini P, Trespidi L, Colombo A, Vendola N, Marchini M, Crosignani PG. A gonadotropin-releasing hormone agonist versus a low-dose oral contraceptive for pelvic pain associated with endometriosis. Fertility and sterility. 1993;60(1):75-9. [DOI:10.1016/S0015-0282(16)56039-7]
10. Xue Q, Lin Z, Cheng Y-H, Huang C-C, Marsh E, Yin P, et al. Promoter Methylation Regulates Estrogen Receptor 2 in Human Endometrium and Endometriosis 1. Biology of reproduction. 2007;77(4):681-7. [DOI:10.1095/biolreprod.107.061804]
11. Xue Q, Lin Z, Yin P, Milad MP, Cheng Y-H, Confino E, et al. Transcriptional activation of steroidogenic factor-1 by hypomethylation of the 5′ CpG island in endometriosis. The Journal of Clinical Endocrinology & Metabolism. 2007;92(8):3261-7. [DOI:10.1210/jc.2007-0494]
12. Smith CJ, Ryckman KK. Epigenetic and developmental influences on the risk of obesity, diabetes, and metabolic syndrome. Diabetes, metabolic syndrome and obesity: targets and therapy. 2015;8:295. [DOI:10.2147/DMSO.S61296]
13. Nugent BM, Bale TL. The omniscient placenta: metabolic and epigenetic regulation of fetal programming. Frontiers in Neuroendocrinology. 2015;39:28-37. [DOI:10.1016/j.yfrne.2015.09.001]
14. Chan RWS, Ng EHY, Yeung WSB. Identification of cells with colony-forming activity, self-renewal capacity, and multipotency in ovarian endometriosis. The American journal of pathology. 2011;178(6):2832-44. [DOI:10.1016/j.ajpath.2011.02.025]
15. Moore LD, Le T, Fan G. DNA methylation and its basic function. Neuropsychopharmacology. 2013;38(1):23-38. [DOI:10.1038/npp.2012.112]
16. Xu F, Mao C, Ding Y, Rui C, Wu L, Shi A, et al. Molecular and enzymatic profiles of mammalian DNA methyltransferases: structures and targets for drugs. Current medicinal chemistry. 2010;17(33):4052-71. [DOI:10.2174/092986710793205372]
17. Jeltsch A. Molecular enzymology of mammalian DNA methyltransferases. DNA Methylation: Basic Mechanisms: Springer; 2006. p. 203-25. [DOI:10.1007/3-540-31390-7_7]
18. Bird AP. CpG-rich islands and the function of DNA methylation. Nature. 1986;321:209-13. [DOI:10.1038/321209a0]
19. Costello JF, Plass C. Methylation matters. Journal of medical genetics. 2001;38(5):285-303. [DOI:10.1136/jmg.38.5.285]
20. Koukoura O, Sifakis S, Spandidos DA. DNA methylation in the human placenta and fetal growth (review). Molecular medicine reports. 2012;5(4):883-9. [DOI:10.3892/mmr.2012.763]
21. Zeitoun K, Takayama K, Michael MD, Bulun SE. Stimulation of aromatase P450 promoter (II) activity in endometriosis and its inhibition in endometrium are regulated by competitive binding of steroidogenic factor-1 and chicken ovalbumin upstream promoter transcription factor to the same cis-acting element. Molecular endocrinology. 1999;13(2):239-53. [DOI:10.1210/mend.13.2.0229]
22. Rice DA, Mouw AR, Bogerd AM, Parker KL. A shared promoter element regulates the expression of three steridogenic enzymes. Molecular endocrinology. 1991;5(10):1552-61. [DOI:10.1210/mend-5-10-1552]
23. Morohashi K, Honda S, Inomata Y, Handa H, Omura T. A common trans-acting factor, Ad4-binding protein, to the promoters of steroidogenic P-450s. Journal of Biological Chemistry. 1992;267(25):17913-9.
24. Tian Y, Kong B, Zhu W, Su S, Kan Y. Expression of steroidogenic factor 1 (SF-1) and steroidogenic acute regulatory protein (StAR) in endometriosis is associated with endometriosis severity. Journal of International Medical Research. 2009;37(5):1389-95. [DOI:10.1177/147323000903700513]
25. Wojdacz TK, Dobrovic A. Methylation-sensitive high resolution melting (MS-HRM): a new approach for sensitive and high-throughput assessment of methylation. Nucleic acids research. 2007;35(6):e41. [DOI:10.1093/nar/gkm013]
26. Song S-H, Jong H-S, Choi HH, Inoue H, Tanabe T, Kim NK, et al. Transcriptional silencing of cyclooxygenase-2 by hyper-methylation of the 5′ CpG island in human gastric carcinoma cells. Cancer research. 2001;61(11):4628-35.
27. Shao G, Berenguer J, Borczuk AC, Powell CA, Hei TK, Zhao Y. Epigenetic inactivation of Betaig-h3 gene in human cancer cells. Cancer research. 2006;66(9):4566-73. [DOI:10.1158/0008-5472.CAN-05-2130]
28. Zhu X, Leav I, Leung Y-k, Wu M, Liu Q, Gao Y, et al. Dynamic regulation of estrogen receptor-β expression by DNA methylation during prostate cancer development and metastasis. The American journal of pathology. 2004;164(6):2003-12. [DOI:10.1016/S0002-9440(10)63760-1]
29. Honda H, Pazin MJ, Ji H, Wernyj RP, Morin PJ. Crucial roles of Sp1 and epigenetic modifications in the regulation of the CLDN4 promoter in ovarian cancer cells. Journal of Biological Chemistry. 2006;281(30):21433-44. [DOI:10.1074/jbc.M603767200]
30. Wu H, Chen Y, Liang J, Shi B, Wu G, Zhang Y, et al. Hypomethylation-linked activation of PAX2 mediates tamoxifen-stimulated endometrial carcinogenesis. Nature. 2005;438(7070):981-7. [DOI:10.1038/nature04225]
31. Sekhon RS, Peterson T, Chopra S. Epigenetic modifications of distinct sequences of the p1 regulatory gene specify tissue-specific expression patterns in maize. Genetics. 2007;175(3):1059-70. [DOI:10.1534/genetics.106.066134]
32. Wade PA. Methyl CpG‐binding proteins and transcriptional repression. Bioessays. 2001;23(12):1131-7. [DOI:10.1002/bies.10008]
33. Bird AP, Wolffe AP. Methylation-induced repression-belts, braces, and chromatin. Cell. 1999;99(5):451-4. [DOI:10.1016/S0092-8674(00)81532-9]
34. Zhang X-Y, Ehrlich KC, Wang RY-H, Ehrlich M. Effect of site-specific DNA methylation and mutagenesis on recognition by methylated DNA-binding protein from human placenta. Nucleic acids research. 1986;14(21):8387-97. [DOI:10.1093/nar/14.21.8387]
35. Nan X, Campoy FJ, Bird A. MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin. Cell. 1997;88(4):471-81. [DOI:10.1016/S0092-8674(00)81887-5]
36. Shen JH-C, Ingraham HA. Regulation of the orphan nuclear receptor steroidogenic factor 1 by Sox proteins. Molecular Endocrinology. 2002;16(3):529-40. [DOI:10.1210/mend.16.3.0782]
37. Daggett MA, Rice DA, Heckert LL. Expression of steroidogenic factor 1 in the testis requires an E box and CCAAT box in its promoter proximal region. Biology of reproduction. 2000;62(3):670-9. [DOI:10.1095/biolreprod62.3.670]
38. Harris AN, Mellon PL. The basic helix-loop-helix, leucine zipper transcription factor, USF (upstream stimulatory factor), is a key regulator of SF-1 (steroidogenic factor-1) gene expression in pituitary gonadotrope and steroidogenic cells. Molecular Endocrinology. 1998;12(5):714-26. [DOI:10.1210/mend.12.5.0100]
39. Nomura M, Bärtsch S, Nawata H, Omura T, Morohashi K-i. An E box element is required for the expression of the ad4bp gene, a mammalian homologue of ftz-f1 gene, which is essential for adrenal and gonadal development. Journal of Biological Chemistry. 1995;270(13):7453-61. [DOI:10.1074/jbc.270.13.7453]
40. Illingworth R, Kerr A, DeSousa D, Jørgensen H, Ellis P, Stalker J, et al. A novel CpG island set identifies tissue-specific methylation at developmental gene loci. PLoS biology. 2008;6(1):e22. [DOI:10.1371/journal.pbio.0060022]
41. Weber M, Davies JJ, Wittig D, Oakeley EJ, Haase M, Lam WL, et al. Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nature genetics. 2005;37(8):853-62. [DOI:10.1038/ng1598]
42. Shen L, Kondo Y, Guo Y, Zhang J, Zhang L, Ahmed S, et al. Genome-wide profiling of DNA methylation reveals a class of normally methylated CpG island promoters. PLoS genetics. 2007;3(10):e181. [DOI:10.1371/journal.pgen.0030181]
43. Anier K, Malinovskaja K, Aonurm-Helm A, Zharkovsky A, Kalda A. DNA methylation regulates cocaine-induced behavioral sensitization in mice. Neuropsychopharmacology. 2010;35(12):2450-61. [DOI:10.1038/npp.2010.128]
44. Bélanger A-S, Tojcic J, Harvey M, Guillemette C. Regulation of UGT1A1 and HNF1 transcription factor gene expression by DNA methylation in colon cancer cells. BMC molecular biology. 2010;11(1):9. [DOI:10.1186/1471-2199-11-9]
45. Song F, Mahmood S, Ghosh S, Liang P, Smiraglia DJ, Nagase H, et al. Tissue specific differentially methylated regions (TDMR): Changes in DNA methylation during development. Genomics. 2009;93(2):130-9. [DOI:10.1016/j.ygeno.2008.09.003]
46. Lin Z, Reierstad S, Huang C-C, Bulun SE. Novel estrogen receptor-α binding sites and estradiol target genes identified by chromatin immunoprecipitation cloning in breast cancer. Cancer research. 2007;67(10):5017-24. [DOI:10.1158/0008-5472.CAN-06-3696]
47. Wang Q, Carroll JS, Brown M. Spatial and temporal recruitment of androgen receptor and its coactivators involves chromosomal looping and polymerase tracking. Molecular cell. 2005;19(5):631-42. [DOI:10.1016/j.molcel.2005.07.018]
48. Stevens TA, Iacovoni JS, Edelman DB, Meech R. Identification of novel binding elements and gene targets for the homeodomain protein BARX2. Journal of Biological Chemistry. 2004;279(15):14520-30. [DOI:10.1074/jbc.M310259200]
49. Hoivik EA, Aumo L, Aesoy R, Lillefosse H, Lewis AlE, Perrett RM, et al. Deoxyribonucleic acid methylation controls cell type-specific expression of steroidogenic factor 1. Endocrinology. 2008;149(11):5599-609. [DOI:10.1210/en.2008-0104]
50. Xue Q, Zhou YF, Zhu SN, Bulun SE. Hypermethylation of the CpG island spanning from exon II to intron III is associated with steroidogenic factor 1 expression in stromal cells of endometriosis. Reproductive Sciences. 2011;18(11):1080-4. [DOI:10.1177/1933719111404614]
51. Xue Q, Xu Y, Yang H, Zhang L, Shang J, Zeng C, et al. Methylation of a novel CpG island of intron 1 is associated with steroidogenic factor 1 expression in endometriotic stromal cells. Reproductive Sciences. 2013:1933719113497283. [DOI:10.1177/1933719113497283]
52. Yamagata Y, Nishino K, Takaki E, Sato S, Maekawa R, Nakai A, et al. Genome-wide DNA methylation profiling in cultured eutopic and ectopic endometrial stromal cells. PloS one. 2014;9(1):e83612. [DOI:10.1371/journal.pone.0083612]

Add your comments about this article : Your username or Email:

Send email to the article author

© 2019 All Rights Reserved | Jorjani Biomedicine Journal

Designed & Developed by : Yektaweb