Endometriosis and Epigenetics: What do we Know?

Crossmark: check for updates

Authors

  • Joseph Nassif, MD Department of Obstetrics and Gynecology, American University of Beirut Medical Center (AUBMC), Beirut, Lebanon
  • Ali Khalil, MD Department of Obstetrics and Gynecology, American University of Beirut Medical Center (AUBMC), Beirut, Lebanon
  • Naji Aswad, MD Department of Obstetrics and Gynecology, American University of Beirut Medical Center (AUBMC), Beirut, Lebanon
  • Antoine Abu Musa, MD, PhD Department of Obstetrics and Gynecology, American University of Beirut Medical Center (AUBMC), Beirut, Lebanon
  • Georges Rameh, MD Department of Obstetrics and Gynecology, American University of Beirut Medical Center (AUBMC), Beirut, Lebanon

DOI:

https://doi.org/10.17140/WHOJ-4-125

Keywords:

Endometriosis; Epigenetics; DNA methylation; Histone acetylation; Immunologic dysregulation; micro RNA expression

Abstract

Objective
Endometriosis is a common gynecological condition with a pathogenesis that is multifactorial and not well understood. The aim
of this review was to explore the multiplicity of epigenetic changes in the field of this disease.
Main Findings
Epigenetic alterations in endometriosis may be classified into four main categories, with cross-reactions between these changes as
well as genetic, environmental, hormonal factors, etc. Deoxyribonucleic acid (DNA) hypomethylation and hypermethylation control the transcription of several genes leading to the progression of this condition. Micro RNAs (miRNA) dysregulation controls
ribonucleic acid (RNA) translation, degradation, and splicing. Immunologic changes involved downregulate the ability of immune
cells to target shed cells. Furthermore, histone hypoacetylation and hyperacetylation affect the metabolism of steroids.
Conclusion
Endometriosis pathogenesis is a very wide and complex subject, associating several hypotheses. The epigenetic pathways discussed
in this review may be the target of new more effective treatments in this field.

References

Vercellini P, Viganò P, Somigliana E, Fedele L. Endometriosis: Pathogenesis and treatment. Nat Rev Endocrinol. 2014; 10(5): 261- 275. doi: 10.1038/nrendo.2013.255

Jensen JRM, Coddington CCIM. Evolving spectrum: The patho-genesis of endometriosis. Clin Obstet Gynecol. 2010; 53(2): 379-388. doi: 10.1097/GRF.0b013e3181db7b84

Sourial S, Tempest N, Hapangama DK. Theories on the patho-genesis of endometriosis. Int J Reprod Med. 2014; 2014: 179515. doi: 10.1155/2014/179515

Christodoulakos G, Augoulea A, Lambrinoudaki I, Sioulas V, Creatsas G. Pathogenesis of endometriosis: The role of defec-tive immunosurveillance. Eur J Contracept Reprod Health Care. 2007; 12(3): 194-202.

Semino C, Semino A, Pietra G, et al. Role of major histocompat-ibility complex class I expression and natural killer-like T cells in the genetic control of endometriosis. Fertil Steril. 1995; 64(5): 909- 916. doi: 10.1016/S0015-0282(16)57901-1

Hapangama DK, Turner MA, Drury J, et al. Aberrant expression of regulators of cell-fate found in eutopic endometrium is found in matched ectopic endometrium among women and in a baboon model of endometriosis. Hum Reprod. 2010; 25(11): 2840-2850. doi: 10.1093/humrep/deq248

Burney RO, Giudice L. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012; 98: 511-519. doi: 10.1016/j.fertn-stert.2012.06.029

Bogdanovic O, Veenstra GJ. DNA methylation and methyl-CpG binding proteins: Developmental requirements and function. Chro-mosoma. 2009; 118: 549-565. doi: 10.1007/s00412-009-0221-9

Ting AH, Jair KW, Suzuki H, Yen RW, Baylin SB, Schuebel KE. Mammalian DNA methyltransferase 1: Inspiration for new direc-tions. Cell Cycle. 2004; 3: 1024-1026. doi: 10.4161/cc.3.8.1070

Hsiao KY, Wu MH, Chang N, et al. Coordination of AUF1 and miR-148a destabilizes DNA methyltransferase 1 mRNA under hypoxia in endometriosis. Mol Hum Reprod. 2015; 21: 894-904. doi: 10.1093/molehr/gav054

Arosh JA, Lee J, Starzinski-Powitz A, Banu SK. Selective inhibi-Review | Volume 4 | Number 1| tion of prostaglandin E2 receptors EP2 and EP4 modulates DNA methylation and histone modification machinery proteins in hu-man endometriotic cells. Mol Cell Endocrinol. 2015; 409: 51-58. doi: 10.1016/j.mce.2015.03.023

Tsai SJ, Wu MH, Lin CC, Sun HS, Chen HM. Regulation of ste-roidogenic acute regulatory protein expression and progesterone production in endometriotic stromal cells. J Clin Endocrinol Metab. 2001; 86: 5765-5773. doi: 10.1210/jcem.86.12.8082

Wang D, Chen Q, Zhang C, Ren F, Li T. DNA hypomethylation of the COX-2 gene promoter is associated with up-regulation of its mRNA expression in eutopic endometrium of endometriosis. Eur J Med Res. 2012; 17: 12. doi: 10.1186/2047-783X-17-12

Yamagata Y, Nishino K, Takaki E, et al. Genome-wide DNA methylation profiling in cultured eutopic and ectopic endometrial stromal cells. PLoS One. 2014; 9: e83612. doi: 10.1371/journal. pone.0083612

Wu Y, Strawn E, Basir Z, Halverson G, Guo SW. Promoter hypermethylation of progesterone receptor isoform B (PR-B) in endometriosis. Epigenetics. 2006; 1: 106-111.

Wu Y, Starzinski-Powitz A, Guo SW. Prolonged stimulation with tumor necrosis factor-alpha induced partial methylation at PR-B promoter in immortalized epithelial-like endometriotic cells. Fertil Steril. 2008; 90: 234-237. doi: 10.1016/j.fertnstert.2007.06.008

Wu Y, Starzinski-Powitz A, Guo SW. Trichostatin A, a histone deacetylase inhibitor, attenuates invasiveness and reactivates E-cadherin expression in immortalized endometriotic cells. Reprod Sci. 2007; 14: 374-382. doi: 10.1177/1933719107302913

Wu Y, Halverson G, Basir Z, Strawn E, Yan P, Guo SW. Aber-rant methylation at HOXA10 may be responsible for its aberrant expression in the endometrium of patients with endometriosis. Am J Obstet Gynecol. 2005; 193: 371-380. doi: 10.1016/j.ajog.2005.01.034

Dyson MT, Roqueiro D, Monsivais D, et al. Genome-wide DNA methylation analysis predicts an epigenetic switch for GATA factor expression in endometriosis. PLoS Genet. 2014; 10(3): e1004158. doi: 10.1371/journal.pgen.1004158

Hsiao KY, Wu MH, Tsai SJ. Epigenetic regulation of the patho-logical process in endometriosis. Reprod Med Biol. 2017; 16: 314- 319. doi: 10.1002/rmb2.12047

Shen L, Yang S, Huang W, et al. MicroRNA23a and microRN-A23b deregulation depresses SF-1 and upregulates estrogen sig-naling in ovarian endometriosis. J Clin Endocrinol Metab. 2013; 98: 1575-1582. doi: 10.1210/jc.2012-3010

Lin SC, Wang CC, Wu MH, Yang SH, Li YH, Tsai SJ. Hypoxia-Submit your article to this journal | https://openventio.org/submit-manuscript/ Review | Volume 4 | Number 1| Rameh G, et al induced microRNA-20a expression increases ERK phosphoryla-tion and angiogenic gene expression in endometriotic stromal cells. J Clin Endocrinol Metab. 2012; 97: E1515-E1523. doi: 10.1210/ jc.2012-1450

Abe W, Nasu K, Nakada C, Kawano Y, Moriyama M, Narahara H. miR-196b targets c-myc and Bcl-2 expression, inhibits prolif-eration and induces apoptosis in endometriotic stromal cells. Hum Reprod. 2013; 28: 750-761. doi: 10.1093/humrep/des446

Bianco B, André GM, Vilarino FL, Peluso C, Mafra FA, Christofolini DM, Barbosa CP. The possible role of genetic vari-ants in autoimmune related genes in the development of endo-metriosis. Hum Immunol. 2012; 73: 306-315. doi: 10.1016/j.hu-mimm.2011.12.009

Lu Q. The critical importance of epigenetics in autoimmunity. J Autoimmun. 2013; 41: 1-5. doi: 10.1016/j.jaut.2013.01.010

Chen S, Zhang J, Huang C, Lu W, Liang Y, Wan X. Expression of the T regulatory cell transcription factor FoxP3 in peri-implan-tation phase endometrium in infertile women with endometriosis. Reprod Biol Endocrinol. 2012; 10: 34. doi: 10.1186/1477-7827-10-34

Fernandez RM, Noval JA, Garcia-Lozano JC, Borrego S, Mo-lini JL, Antinolo G. Polymorphisms in the promoter regions of FAS and FASL genes as candidate genetic factors conferring sus-ceptibility to endometriosis. Int J Mol Med. 2005; 15: 865-869. doi: 10.3892/ijmm.15.5.865

Nishida M, Nasu K, Ueda T, Fukuda J, Takai N, Miyakawa I. Endometriotic cells are resistant to interferon-gamma-induced cell growth inhibition and apoptosis: A possible mechanism involved in the pathogenesis of endometriosis. Mol Hum Reprod. 2005; 11: 29-34. doi: 10.1093/molehr/gah133

Kim SH, Ihm HJ, Oh YS, Chae HD, Kim CH, Kang BM. In-creased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis. Am J Reprod Immunol. 2013; 70: 497-508. doi: 10.1111/aji.12161

Colon-Diaz M, Baez-Vega P, Garcia M, et al. HDAC1 and HDAC2 are differentially expressed in endometriosis. Reprod Sci. 2012; 19: 483-492. doi: 10.1177/1933719111432870

Monteiro JB, Colón-Díaz M, García M, et al. Endometri-osis is characterized by a distinct pattern of histone 3 and his-tone 4 lysine modifications. Reprod Sci. 2014; 21(3): 305-318. doi: 10.1177/1933719113497267

Colón-Caraballo M, Monteiro JB, Flores I. H3K27me3 is an epigenetic mark of relevance in endometriosis. Reprod Sci. 2015; 22(9): 1134-1142. doi: 10.1177/1933719115578924

Downloads

Published

2018-03-05

How to Cite

Joseph Nassif, MD, Ali Khalil, MD, Naji Aswad, MD, Antoine Abu Musa, MD, PhD, & Georges Rameh, MD. (2018). Endometriosis and Epigenetics: What do we Know?. Women’s Health, 1–7. https://doi.org/10.17140/WHOJ-4-125

Issue

Volume 4 Issue 1 2018

Section

Articles

License

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

All content published in Women's Health (WH) is licensed under the Creative Commons Attribution 4.0 International License (CC BY 4.0). This license allows anyone to copy, distribute, transmit, and adapt the work — including for commercial purposes — provided appropriate credit is given to the original author(s) and source.

Most read articles by the same author(s)