Volume 17, Issue 3 (March 2019 2019)                   IJRM 2019, 17(3): 185-194 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Mousazadeh S, Ghaheri A, Shahhoseini M, Aflatoonian R, Afsharian P. Differential expression of progesterone receptor isoforms related to PGR +331g/a polymorphism in endometriosis: A case-control study. IJRM 2019; 17 (3) :185-194
URL: http://ijrm.ir/article-1-1451-en.html
Differential expression of progesterone receptor isoforms related to PGR +331g/a polymorphism in endometriosis: A case-control study
Sepideh Mousazadeh1 , Azadeh Ghaheri2 , Maryam Shahhoseini3 , Reza Aflatoonian4 , Parvaneh Afsharian * 5
1- Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
2- Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
3- Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
4- Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
5- Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran , pafshar@royaninstitute.org
Abstract:   (2618 Views)
Background: Endometriosis are defined as a progesterone-resistance disease. Two progesterone receptor (PR) isoforms, namely PR-A and PR-B, mediate the special effects of progesterone. One of the most effective polymorphism in the promoter region of PGR is the +331G/A.
Objective: The differential expression level of PR isoforms due to +331G/A polymorphism may be able to influence the function of progesterone and reduce the susceptibility of endometriosis.
Materials and Methods: This analytic, case-control study was carried out at Royan Institute, Tehran, Iran. Whole-blood samples were collected from 98 infertile women undergoing laparoscopy for endometriosis and 102 healthy fertile women. After DNA extraction, genotype frequencies were determined by polymerase chain reactionrestriction fragment length polymorphism. Then, RNA was extracted from the selected eutopic tissue samples of endometriosis patients. Analysis of PR-A and PR-B mRNA expressions were performed using Real-time polymerase chain reaction.
Results: The frequency distribution of GG, GA genotypes in +331G/A polymorphism was 98.04%, 1.96% in the patients and 97.96%, 2.04% in the control groups, respectively (p= 0.968). Although our data did not show any significant association with +331G/A in the patient and control groups, we were able to demonstrate significantly highe expression level of PR-B and no significant lower expression level of PR-A isoforms in patients by favoring GA to GG genotypes (p= 0.017, p= 0.731, respectively).
Conclusion: Our findings show that patients with GA genotypes had a higher expression level of PR-B compared to patients with GG genotypes.
Keywords: Endometriosis, Progesterone receptor A, Progesterone receptor B, rs10895068.
Full-Text [PDF 341 kb]   (924 Downloads) |   |   Full-Text (HTML)  (454 Views)  
Type of Study: Original Article |
References
1. [1] Practice Committee of American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss: a committee opinion. Fertil Steril 2013; 99: 63. [DOI:10.1016/j.fertnstert.2012.09.023]
2. [2] Pincus G. The control of fertility. Elsevier; New York, London 2013.
3. [3] Macer ML, Taylor HS. Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosisassociated infertility. Obstet Gynecol Clin North Am 2012; 39: 535-549. [DOI:10.1016/j.ogc.2012.10.002]
4. [4] Nothnick WB. The emerging use of aromatase inhibitors for endometriosis treatment. Reprod Biol Endocrinol 2011; 9: 87-95. [DOI:10.1186/1477-7827-9-87]
5. [5] Abrão MS, Podgaec S, Filho BM, Ramos LO, Pinotti JA, de Oliveira RM. The use of biochemical markers in the diagnosis of pelvic endometriosis. Hum Reprod 1997; 12: 2523-2527. [DOI:10.1093/humrep/12.11.2523]
6. [6] Lin X, Wei ML, Tong XM, Xu WH, Zhou F, Huang QX, et al. Outcome of in vitro fertilization in endometriosisassociated infertility: a 5-year database cohort study. Chin Med J 2012; 125: 2688-2693.
7. [7] Bulletti C, Coccia ME, Battistoni S, Borini A. Endometriosis and infertility. J Assist Reprod Genet 2010; 27: 441-447. [DOI:10.1007/s10815-010-9436-1]
8. [8] Tan H, Yi L, Rote NS, Hurd WW, Mesiano S. Progesterone receptor-A and-B have opposite effects on proinflammatory gene expression in human myometrial cells: implications for progesterone actions in human pregnancy and parturition. J Clin Endocrinol Metab 2012; 97: 719-730. [DOI:10.1210/jc.2011-3251]
9. [9] Attia GR, Zeitoun K, Edwards D, Johns A, Carr BR, Bulun SE. Progesterone receptor isoform A but Not B is expressed in endometriosis. J Clin Endocrinol Metab 2000; 85: 2897-2902. [DOI:10.1210/jc.85.8.2897]
10. [10] Lee Y, Sooranna SR, Terzidou V, Christian M, Brosens J, Huhtinen K, et al. Interactions between inflammatory signals and the progesterone receptor in regulating gene expression in pregnant human uterine myocytes. J Cell Mol Med 2012; 16: 2487-2503. [DOI:10.1111/j.1582-4934.2012.01567.x]
11. [11] Near AM, Wu AH, Templeman C, Van Den Berg DJ, Doherty JA, Rossing MA, et al. Progesterone receptor gene polymorphisms and risk of endometriosis: results from an international collaborative effort. Fertil Steril 2011;95: 40-45. [DOI:10.1016/j.fertnstert.2010.06.059]
12. [12] Ludwig AH, Murawska M, Panek G, Timorek A, Kupryjanczyk J. Androgen, progesterone, and FSH receptor polymorphisms in ovarian cancer risk and outcome. Endocr Relat Cancer 2009; 16: 1005-1016. [DOI:10.1677/ERC-08-0135]
13. [13] Bulun SE, Cheng YH, Pavone ME, Xue Q, Attar E, Trukhacheva E, et al. Estrogen receptor-β, estrogen receptor-α, and progesterone resistance in endometriosis. Semin Reprod Med 2010; 28: 36-43. [DOI:10.1055/s-0029-1242991]
14. [14] Bulun SE, Cheng YH, Yin P, Imir G, Utsunomiya H, Attar E, et al. Progesterone resistance in endometriosis: link to failure to metabolize estradiol. Mol Cell Endocrinol 2006; 248: 94-103. [DOI:10.1016/j.mce.2005.11.041]
15. [15] Aljanabi SM, Martinez I. Universal and rapid salt-extraction of high quality genomic DNA for PCR-based techniques. Nucleic Acids Res 1997; 25: 4692-4693. [DOI:10.1093/nar/25.22.4692]
16. [16] Hagan CR, Daniel AR, Dressing GE, Lange CA. Role of phosphorylation in progesterone receptor signaling and specificity. Mol Cell Endocrinol 2012; 357: 43-49. [DOI:10.1016/j.mce.2011.09.017]
17. [17] Conneely OM, Lydon JP. Progesterone receptors in reproduction: functional impact of the A and B isoforms. Steroids 2000; 65: 571-577. [DOI:10.1016/S0039-128X(00)00115-X]
18. [18] Khan JA, Bellance C, Guiochon-Mantel A, Lombès M, Loosfelt H. Differential regulation of breast cancer-associated genes by progesterone receptor isoforms PRA and PRB in a new bi-inducible breast cancer cell line. PloS One 2012;7: e45993-e46012. [DOI:10.1371/journal.pone.0045993]
19. [19] Jacobsen BM, Horwitz KB. Progesterone receptors, their isoforms and progesterone regulated transcription. Mol Cell Endocrinol 2012; 357: 18-29. [DOI:10.1016/j.mce.2011.09.016]
20. [20] Bulun SE, Cheng YH, Pavone ME, Yin P, Imir G, Utsunomiya H, et al. 17β-Hydroxysteroid dehydrogenase-2 deficiency and progesterone resistance in endometriosis. Semin Reprod Med 2010; 28: 44-50. [DOI:10.1055/s-0029-1242992]
21. [21] Hardy DB, Janowski BA, Corey DR, Mendelson CR. Progesterone receptor plays a major antiinflammatory role in human myometrial cells by antagonism of nuclear factor-κB activation of cyclooxygenase 2 expression. Mol Endocrinol 2006; 20: 2724-2733. [DOI:10.1210/me.2006-0112]
22. [22] Eggert-Kruse W, Kiefer I, Beck C, Demirakca T, Strowitzki T. Role for tumor necrosis factor alpha (TNF-α) and interleukin 1-beta (IL-1β) determination in seminal plasma during infertility investigation. Fertil Steril 2007; 87: 810-823. [DOI:10.1016/j.fertnstert.2006.08.103]
23. [23] Dossus L, Canzian F, Kaaks R, Boumertit A, Weiderpass E. No association between progesterone receptor gene+331G/A polymorphism and endometrial cancer. Cancer Epidemiol Biomarkers Prev 2006; 15: 1415-1416. [DOI:10.1158/1055-9965.EPI-06-0215]
24. [24] De Vivo I, Huggins GS, Hankinson SE, Lescault PJ, Boezen M, Colditz GA, et al. A functional polymorphism in the promoter of the progesterone receptor gene associated with endometrial cancer risk. Proc Natl Acad Sci USA 2002; 99: 12263-12268. [DOI:10.1073/pnas.192172299]
25. [25] Chaudhary S, Panda AK, Mishra DR, Mishra SK. Association of+ 331G/A PgR polymorphism with susceptibility to female reproductive cancer: evidence from a metaanalysis. PloS One 2013; 8: e53308-e53315. [DOI:10.1371/journal.pone.0053308]
26. [26] Berchuck A, Schildkraut JM, Wenham RM, Calingaert B, Ali S, Henriott A, et al. Progesterone receptor promoter+331A polymorphism is associated with a reduced risk of endometrioid and clear cell ovarian cancers. Cancer Epidemiol Biomarkers Prev 2004; 13: 2141-2147.
27. [27] Treloar SA, Zhao ZZ, Armitage T, Duffy DL, Wicks J, O'connor DT, et al. Association between polymorphisms in the progesterone receptor gene and endometriosis. Mol Hum Reprod 2005; 11: 641-647. [DOI:10.1093/molehr/gah221]
28. [28] Van Kaam KJ, Romano A, Schouten JP, Dunselman GA, Groothuis PG. Progesterone receptor polymorphism+ 331G/A is associated with a decreased risk of deep infiltrating endometriosis. Hum Reprod 2007; 22: 129-135. [DOI:10.1093/humrep/del325]
29. [29] Gentilini D, Vigano P, Carmignani L, Spinelli M, Busacca M, Di Blasio AM. Progesterone receptor+ 331G/A polymorphism in endometriosis and deep-infiltrating endometriosis. Fertil Steril 2008; 90: 1243-1245. [DOI:10.1016/j.fertnstert.2007.11.034]
30. [30] Rojas PA, May M, Sequeira GR, Elia A, Alvarez M, Martínez P, et al. Progesterone receptor isoform ratio: A breast cancer prognostic and predictive factor for antiprogestin responsiveness. J Natl Cancer Inst 2017; 109: djw317-325. [DOI:10.1093/jnci/djw317]
Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Designed & Developed by : Yektaweb