1- Department of Obstetrics and Gynecology, Zanjan University of Medical Sciences, Zanjan, Iran, 2- Department of Genetics, Reproductive Medicine Research Center, Jihad Academic Reproductive Medicine and Biology Research Institute, Royan Research Institute, Tehran, Iran 3- Department of Anatomy, Iran University of Medical Sciences, Tehran, Iran, , femehra@yahoo.com 4- Department of Endocrinology and Female Infertility, Reproductive Medicine Research Center, Jihad Academic Research Institute of Reproductive Biology and Medical Sciences, Royan Research Institute, Tehran, Iran.
Abstract: (1562 Views)
Background & aim: Among the important factors affecting female infertility, endometriosis (with a prevalence rate of up to 50% in infertile women) has a special place. Endometriosis, which is known as the presence of endometrial glands and stroma outside the uterine tissue, causes a wide range of functional disorders in the process of follicular development and changes in the follicular microenvironment, which ultimately leads to the creation of an egg that is of suitable quality for the formation of The fetus does not have Therefore, the aim of the present study was to determine and investigate post-translational changes of histones, DNA methylation level and ERβ protein level in the genome of cumulus cells of infertile women with endometriosis. Methods: The present case-control study was conducted at the infertility treatment clinic of Royan Research Institute in 2014. Twenty-four patients were divided into two equal groups. Cumulus cells were obtained from 12 infertile patients with endometriosis and 12 women with male factor infertility (as a control group) under ovulation stimulation protocols for intracytoplasmic sperm injection. Extraction of chromatin from cumulus cells was done after stabilization of DNA binding proteins and then cell lysis and preparation of soluble chromatin. The binding and incorporation levels of MeCP2 protein (as DNA methylation marker), two epigenetic markers related to histone modifications (H3K9me2 and H3K9ac), and ERβ protein to chromatin of cumulus cells were evaluated using the corresponding primary antibodies, secondary antibodies conjugated and Nucleosome-ELISA technique. Data were analyzed using independent t-test t and Levene's test. Results: MeCP2 protein incorporation into DNA was significantly higher in the endometriosis group than in the control group. The level of two epigenetic marks H3K9ac and H3K9me2 in the chromatin of cumulus cells of the patient group showed a significant increase compared to the control group (P<0.05). In addition, an increased level of binding of ERβ protein to the genome was observed compared to the control group. Conclusion: Epigenetic changes, including histone hyperacetylation and hypermethylation, and DNA hypermethylation of the whole genome of cumulus cells of patients with endometriosis had occurred, accompanied by an increase in the level of ERβ protein binding. .
Type of Study: Research |
Subject: Gynaecology Received: 2023/04/23 | Accepted: 2023/07/24 | Published: 2023/09/9
References
1. Kennedy S, Bergqvist A, Chapron C, D’Hooghe T, Dunselman G, Greb R, et al. ESHRE guideline for the diagnosis and treatment of endometriosis. Human Reproduction 2005; 20(10): 2698-704.## [DOI:10.1093/humrep/dei135] [PMID]
2. Koninckx PR, Ussia A, Adamyan L, Wattiez A, Gomel V, Martin DC. Pathogenesis of endometriosis: the genetic/epigenetic theory. Fertility and Sterility 2019; 111(2): 327-40. ## [DOI:10.1016/j.fertnstert.2018.10.013] [PMID]
3. Houshdaran S, Nezhat CR, Vo KC, Zelenko Z, Irwin JC, Giudice LC. Aberrant endometrial DNA methylome and associated gene expression in women with endometriosis. Biology of Reproduction 2016; 95(5): 1-16. ## [DOI:10.1095/biolreprod.116.140434] [PMID] []
4. Wu Y, Strawn E, Basir Z, Halverson G, Guo SW. Aberrant expression of deoxyribonucleic acid methyltransferases DNMT1, DNMT3A, and DNMT3B in women with endometriosis. Fertility and Sterility 2007; 87(1): 24-32. ## [DOI:10.1016/j.fertnstert.2006.05.077] [PMID]
5. Nasu K, Kawano Y, Tsukamoto Y, Takano M, Takai N, Li HL, et al. Aberrant DNA methylation status of endometriosis: Epigenetics as the pathogenesis, biomarker and therapeutic target. Journal of Obstetrics and Gynaecology Research 2011; 37(7): 683-95. ## [DOI:10.1111/j.1447-0756.2011.01663.x] [PMID]
6. 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. American Journal of Obstetrics and Gynecology 2005; 193(2): 371-80. ## [DOI:10.1016/j.ajog.2005.01.034] [PMID]
7. Izawa M, Harada T, Taniguchi F, Ohama Y, Takenaka Y, Terakawa N. An epigenetic disorder may cause aberrant expression of aromatase gene in endometriotic stromal cells. Fertility and Sterility 2008; 89: 1390-6. ## [DOI:10.1016/j.fertnstert.2007.03.078] [PMID]
8. Kim TH, Yoo J-Y, Choi K-C, Shin J-H, Leach RE, Fazleabas AT, et al. Loss of HDAC3 results in nonreceptive endometrium and female infertility. Sci Transl Med 2019; 11(474): eaaf7533. ## [DOI:10.1126/scitranslmed.aaf7533] [PMID] []
9. Munro SK, Farquhar CM, Mitchell MD, Ponnampalam AP. Epigenetic regulation of endometrium during the menstrual cycle. Mol Hum Reprod 2010; 16(5): 297-310. ## [DOI:10.1093/molehr/gaq010] [PMID]
10. Bulun SE, Monsavais D, Pavone ME, Dyson M, Xue Q, Attar E, et al., editors. Role of estrogen receptor-β in endometriosis. Seminars in Reproductive Medicine 2012; 30(1): 39-45. ## [DOI:10.1055/s-0031-1299596] [PMID] []
11. Dai B, Rasmussen TP. Global epiproteomic signatures distinguish embryonic stem cells from differentiated cells. Stem Cells 2007; 25(10): 2567-74. ## [DOI:10.1634/stemcells.2007-0131] [PMID]
12. Rezazadeh Valojerdi M, Eftekhari-Yazdi P, Karimian L, Hassani F, Movaghar B. Vitrification versus slow freezing gives excellent survival, post warming embryo morphology and pregnancy outcomes for human cleaved embryos. Journal of Assisted Reproduction and Genetics 2009; 26(6): 347-54. ## [DOI:10.1007/s10815-009-9318-6] [PMID] []
13. Kitajima M, Matsumoto K, Kajimura I, Harada A, Miyashita N, Matsumura A, et al. The Effects of Endometriosis on Ovarian Functions. Endocrines 2021; 2(2): 142-9. ## [DOI:10.3390/endocrines2020014]
14. Simon C, Gutierrez A, Vidal A, De los Santos M, Tarin J, Remohi J, et al. Outcome of patients with endometriosis in assisted reproduction: results from in-vitro fertilization and oocyte donation. Human Reproduction 1994; 9(4): 725-9. ## [DOI:10.1093/oxfordjournals.humrep.a138578] [PMID]
15. Pellicer A, Navarro J, Bosch E, Garrido N, GARCIA‐VELASCO JA, Remohí J, et al. Endometrial quality in infertile women with endometriosis. Annals of the New York Academy of Sciences 2001; 943(1): 122-30. ## [DOI:10.1111/j.1749-6632.2001.tb03796.x] [PMID]
16. Baumann C, Olson M, Wang K, Fazleabas A, De La Fuente R. Arginine methyltransferases mediate an epigenetic ovarian response to endometriosis. Reproduction 2015; 150(4): 297-310. ## [DOI:10.1530/REP-15-0212] [PMID]
17. La Marca A, Nelson S, Sighinolfi G, Manno M, Baraldi E, Roli L, et al. Anti-Müllerian hormone-based prediction model for a live birth in assisted reproduction. Reproductive Biomedicine Online 2011; 22(4): 341-9. ## [DOI:10.1016/j.rbmo.2010.11.005] [PMID]
18. Izawa M, Taniguchi F, Harada T. Epigenetics in endometriosis. Endometriosis: Springer; 2014; 107-23. ## [DOI:10.1007/978-4-431-54421-0_8]
19. Fraga MF, Ballestar E, Montoya G, Taysavang P, Wade PA, Esteller M. The affinity of different MBD proteins for a specific methylated locus depends on their intrinsic binding properties. Nucleic Acids Research 2003; 31(6): 1765-74. ## [DOI:10.1093/nar/gkg249] [PMID] []
20. Morin SJ, Tao X, Marin D, Zhan Y, Landis J, Bedard J, et al. DNA methylation-based age prediction and telomere length in white blood cells and cumulus cells of infertile women with normal or poor response to ovarian stimulation. Aging (Albany NY) 2018; 10(12): 3761. ## [DOI:10.18632/aging.101670] [PMID] []
21. Knight A, Hipp H, Abhari S, Gerkowicz S, Katler Q, McKenzie L, et al. Markers of ovarian reserve are associated with reproductive age acceleration in granulosa cells from IVF patients. Human Reproduction 2022; 37(10): 2438-45. ## [DOI:10.1093/humrep/deac178] [PMID] []
22. Olsen KW, Castillo-Fernandez J, Zedeler A, Freiesleben NC, Bungum M, Chan AC, et al. A distinctive epigenetic ageing profile in human granulosa cells. Human Reproduction 2020; 35(6): 1332-45. ## [DOI:10.1093/humrep/deaa071] [PMID]
24. Dago DN, Scafoglio C, Rinaldi A, Memoli D, Giurato G, Nassa G, et al. Estrogen receptor beta impacts hormone-induced alternative mRNA splicing in breast cancer cells. BMC Qenomics 2015; 16(1): 1. ## [DOI:10.1186/s12864-015-1541-1] [PMID] []
25. Hervouet E, Cartron PF, Jouvenot M, Delage-Mourroux R. Epigenetic regulation of estrogen signaling in breast cancer. Epigenetics 2013; 8(3): 237-45. ## [DOI:10.4161/epi.23790] [PMID] []
26. Guglielmotto M, Reineri S, Iannello A, Ferrero G, Vanzan L, Miano V, et al. E2 regulates epigenetic signature on Neuroglobin enhancer-promoter in neuronal cells. Frontiers in Cellular Neuroscience 2016; 10: 147. ## [DOI:10.3389/fncel.2016.00147] [PMID] []
27. Wolffe AP. Chromatin remodeling regulated by steroid and nuclear receptors. Cell Research 1997; 7(2): 127-42. ## [DOI:10.1038/cr.1997.14] [PMID]
28. Hosseini E, Mehraein F, Shahhoseini M, Karimian L, Nikmard F, Ashrafi M, et al. Epigenetic alterations of CYP19A1 gene in Cumulus cells and its relevance to infertility in endometriosis. Journal of Assisted Reproduction and Genetics 2016; 33(8): 1105-13. ## [DOI:10.1007/s10815-016-0727-z] [PMID] []
Hosseini E, Shahhosseini M, Afsharian P, Mehrayin F, Ashrafi M, Aflatoonian R. Investigating Post-translational Changes of Histones, DNA Methylation Level, and ERβ Protein Level in the Cumulus Cell Genome of Infertile Women with Endometriosis. armaghanj 2023; 28 (5) :689-703 URL: http://armaghanj.yums.ac.ir/article-1-3470-en.html