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Epigenetic Dynamics of HOXA10 Gene in Infertile Women With Endometriosis

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Abstract

Endometriosis, which has been considered an epigenetic disease, is a prevalent gynecological disorder worldwide. With an emphasis on changes in the HOXA10 gene expression of the endometrium of women with endometriosis, the aim of this study was to investigate HOXA10 gene expression and its correlation with the epigenetic characteristics of the specific promoter region of the gene in the eutopic and ectopic endometrium of women with endometriosis. Thirty-six patients and 21 healthy fertile women were recruited as participants of this study. In this study group, chromatin immunoprecipitation and real-time polymerase chain reaction technique were performed to quantify the epigenetic profile of HOXA10, parallel to its expression. During the secretory phase in eutopic tissues, reduction in HOXA10 gene expression was identified along with lower acetylation and higher methylation of H3K9 as well as higher incorporation of MeCP2 on the HOXA10 gene promoter. In contrast with control group, studies of ectopic endometriotic lesions in the secretory phase demonstrate a correlation between induction of HOXA10 gene and higher levels of H3K9ac, H3K27me3, and H3K4me3 in the promoter region of the HOXA10 gene. Further distinctions from the control group were revealed in the proliferative phase of the ectopic endometrium, where upregulation of HOXA10 coincided with lower incorporation of MeCP2 and higher levels of H3K4me3 in the promoter region. Since it is well known that aberrant expression of HOXA10 is involved in pathogenesis of the endometrium, our data emphasized the epigenetic role of this gene aberration related to clinical pathophysiology of endometriosis.

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References

  1. Signorile PG, Baldi A. New evidence in endometriosis. Int J Biochem Cell Biol. 2015;60:19–22.

    CAS  PubMed  Google Scholar 

  2. Guo SW. Epigenetics of endometriosis. Mol Hum Reprod. 2009; 15(10):587–607.

    CAS  PubMed  Google Scholar 

  3. Berger SL, Kouzarides T, Shiekhattar R, Shilatifard A. An operational definition of epigenetics. Genes Dev. 2009;23(7):781–783.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Laird PW, Jaenisch R. The role of DNA methylation in cancer genetic and epigenetics. Annu Rev Genet. 1996;30:441–464.

    CAS  PubMed  Google Scholar 

  5. Nan X, Campoy F, Bird A. MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin. Cell. 1997; 88(4):471–481.

    CAS  PubMed  Google Scholar 

  6. Peterson CL, Laniel MA. Histones and histone modifications. Curr Biol. 2004;14(14):546–551.

    Google Scholar 

  7. Favaedi R, Shahhoseini M, Pakzad M, Mollamohammadi S, Baharvand H. Comparative epigenetic evaluation of human embryonic stem and induced pluripotent cells. Int J Dev Biol. 2016;5:60(4–6):103–110.

    Google Scholar 

  8. Monteiro JB, Colon Diaz M, Garcia M, et al. Endometriosis is characterized by a distinct pattern of histone 3 and histone 4 lysine modifications. Reprod Sci. 2014;21(3):305–318.

    PubMed  PubMed Central  Google Scholar 

  9. Kim JJ, Taylor HS, Lu Z, et al. Altered expression of HOXA10 in endometriosis: potential role in decidualization. Mol Hum Reprod. 2007;13(5);323–332.

    Google Scholar 

  10. Salih SM, Taylor HS. HOXA10 gene expression in human fallopian tube and ectopic pregnancy. Am J Obstet Gynecol. 2004; 190(5):1404–1406.

    CAS  PubMed  Google Scholar 

  11. Sarno JL, Kilman HJ, Taylor HS. HOXA10, Pbx2 and Meis1 protein expression in the human endometrium: formation of multimeric complexes on HOXA10 target genes. J Clin Endocrinol Metab. 2005;90(1);522–528.

    CAS  PubMed  Google Scholar 

  12. Taylor HS, Arici A, Olive D, Igarashi P. HOXA10 is expressed in response to sex steroids at the time of implantation in the human endometrium. J Clin Invest. 1998;101(7):1379–1384.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Daftary GS, Taylor HS. Endocrine regulation of HOX Genes. Endocr Rev. 2006;27(4);331–355.

    CAS  PubMed  Google Scholar 

  14. Godbole G, Suman P, Malik A, et al. Decrease in expression of HOXA10 in the decidua after embryo implantation promotes trophoblast invasion. Endocrinology. 2017;158(8):2618002D2633. doi:10.1210/en.2017–00032.

    Google Scholar 

  15. Szczepanska M, Wirstlein P, Luczak M, Jagodzinski PP, Skrzypczak J. Reduced expression of HOXA10 in the midluteal endometrium from infertile women with minimal endometriosis. Biomed Pharmacother. 2010;64(10);697–705.

    CAS  PubMed  Google Scholar 

  16. Wu Y, Halverson G, Basir Z, Strawn E, Yan P, Guo SW. Aberrant methylation at HOXA10 may be responsible for its aberrant expression in the endometrium of patients with endometriosis. Am J Obstet Gynecol. 2005;193(2);371–380.

    CAS  Google Scholar 

  17. Noyes RW, Hertig AT, Rock J. Dating the endometrial biopsy. Fertil Steril. 1950;1:3–25

    Google Scholar 

  18. Monkkonen KS, Aflatoonian R, Lee KF, et al. Localization and variable expression of Gai2 in human endometrium and Fallopian tubes. Hum Reprod. 2007;22(5);1224–1230.

    CAS  PubMed  Google Scholar 

  19. Curry TE Jr, Osteen KG. The matrix metalloprotein system: changes, regulation, and impact throughout the ovarian and uterine reproductive cycle. Endocr Rev. 2003;24(4);428–465.

    CAS  PubMed  Google Scholar 

  20. Gui Y, Zhang J, Yuan L, Lessey BA. Regulation of HOXA10 and its expression in normal and abnormal endometrium. Mol Hum Reprod. 1999;5(9);866–873.

    CAS  PubMed  Google Scholar 

  21. Chen C, Zhao M, Yin N, et al. Abnormal histone acetylation and methylation levels in esophageal squamous cell carcinomas. Cancer Invest. 2011;29(8);548–556.

    CAS  PubMed  Google Scholar 

  22. Taby R, Issa JP. Cancer epigenetics. CA Cancer J Clin. 2010; 60(6):376–392.

    PubMed  Google Scholar 

  23. Lee B, Du H, Taylor HS. Experimental murine endometriosis induces DNA methylation and altered gene expression in eutopic endometrium. Biol Reprod. 2009;80(1);79–85.

    PubMed  PubMed Central  Google Scholar 

  24. Naqvi H, Ilagan Y, Krikun G, Taylor HS. Altered genome-wide methylation in endometriosis. Reprod Sci. 2014;21(10): 1237–1243

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Arosh JA, Lee J, Starzinski-Powitz A, Banu SK. Selective inhibition of prostaglandin E2 receptors EP2 and EP4 modulates DNA methylation and histone modification machinery proteins in human endometriotic cells. Mol Cell Endocrinol. 2015;409:51–58

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Kulp JL, Mamillapalli R, Taylor HS. Aberrant HOXA10 Methylation in patients with common gynecologic disorders: implications for reproductive outcomes. Reprod Sci. 2016;23(4);455–463.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Yoshida H, Broaddus R, Cheng W, Xie S, Naora H. Deregulation of the HOXA10 homeobox gene in endometrial carcinoma: role in epithelial-mesenchymal transition. Cancer Res. 2006;66(2); 889–897.

    Google Scholar 

  28. Kim TH, Barrera LO, Zheng M, et al. A high-resolution map of active promoters in the human genome. Nature. 2005;436(7052): 876–880

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Laird PW. The power and the promise of DNA methylation markers. Nat Rev Cancer. 2003;3(4);253–266.

    CAS  PubMed  Google Scholar 

  30. Robertson KD, Wolffe AP. DNA methylation in health and disease. Nat Rev Genet. 2000;1(1);9–11.

    Google Scholar 

  31. Ji F, Yang X, He Y, Wang H, Aili A, Ding Y. Aberrant endometrial DNA methylome of homeobox A10 and catechol-O-methyltransferase in endometriosis. J Assist Reprod Genet. 2017;34(3);409–415.

    PubMed  PubMed Central  Google Scholar 

  32. Bromer JG, Wu J, Zhou Y, Taylor HS. Hypermethylation of homeobox A10 by in utero diethylstilbestrol exposure: an epigenetic mechanism for altered developmental programming. Endocrinology. 2009;150(7);3376–3382.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Baker LA, Allis CD, Wang GG. PHD fingers in human diseases: disorders arising frommisinterpreting epigenetic marks. Mutat Res. 2008;647(1–2);3–12.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Wang GG, Allis C, Chi P. Chromatin remodeling and cancer, Part I: Covalent histone modifications. Trends Mol Med. 2007;13(9); 363–372.

    Google Scholar 

  35. Fuks F. DNA methylation and histone modifications: teaming up to silence genes. Curr Opin Genet Dev. 2005;15(5);490–495.

    CAS  PubMed  Google Scholar 

  36. Lachner M, Jenuwein T. The many faces of histone lysine methylation. Curr Opin Cell Biol 2002;14(3);286–298.

    CAS  PubMed  Google Scholar 

  37. Colón-Caraballo M, Monteiro JB, Flores I. H3K27me3 is an Epigenetic Mark of Relevance in Endometriosis. Reprod Sci. 2015; 22(9):1134–1142.

    PubMed  PubMed Central  Google Scholar 

  38. Lan F, Bayliss P, Rinn JL, et al. Histone H3 lysine 27 demethylase regulates animal posterior development. Nature. 2007;449(7163); 689–694.

    CAS  PubMed  Google Scholar 

  39. Cui P, Liu W, Zhao Y, et al. Comparative analyses of H3K4 and H3K27 trimethylations between the mouse cerebrum and testis. Genomics Proteomics Bioinformatics. 2012;10(2);82–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Hsiao KY, Wu MH, Tsai SJ. Epigenetic regulation of the pathological process in endometriosis. Reprod Med Biol. 2017;16(4); 314–316.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Sood S, Srinivasan R. Alterations in gene promoter methylation and transcript expression induced by cisplatin in comparison to 5-Azacytidine in HeLa and SiHa cervical cancer cell lines. Mol Cell Biochem. 2015;404(1–2):181–191.

    CAS  PubMed  Google Scholar 

  42. Saraswat L, Ayansina D, Cooper KG, Bhattacharya S, Horne AW. Impact of endometriosis on risk of further gynaecological surgery and cancer: a national cohort study. BJOG. 2017 Sep 27.

    Google Scholar 

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Correspondence to Reza Aflatoonian MDPhD or Maryam Shahhoseini PhD.

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Samadieh, Y., Favaedi, R., Ramezanali, F. et al. Epigenetic Dynamics of HOXA10 Gene in Infertile Women With Endometriosis. Reprod. Sci. 26, 88–96 (2019). https://doi.org/10.1177/1933719118766255

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