Influence of Ovarian Endometrioma on Expression of Steroid Receptor RNA Activator, Estrogen Receptors, Vascular Endothelial Growth Factor, and Thrombospondin 1 in the Surrounding Ovarian Tissues

This study investigates the influence of ovarian endometrioma on expression of steroid receptor RNA activator (SRA), estrogen receptors (ERs), vascular endothelial growth factor (VEGF), and thrombospondin 1 (TSP-1) in the surrounding ovarian tissues. Taken from the women with ovarian endometrioma and mature teratoma during laparoscopy, the biopsies were analyzed by real-time polymerase chain reaction and Western blot. Our results indicated that ovarian tissues surrounding endometrioma had lower SRA and ER-α levels but higher SRA protein (SRAP) and ER-β levels than ovarian endometrioma. With lower VEGF levels and higher TSP-1 levels, the surrounding ovarian tissues showed higher expression levels of SRA, SRAP, ER-α, and ER-β in the ovarian endometrioma group when compared to the controls. These data showed that ovarian endometrioma increases SRA, ERs, and TSP-1 but decreases VEGF levels in the surrounding ovarian tissues, suggesting that abnormal expression of these molecules may affect biological behaviors of ovarian endometrioma. Similar content being viewed by others

Daniell JF, Kurtz BR, Gurley LD. Laser laparoscopic management of large endometriomas. Fertil Steril. 1991;55(4):692–695. Donnez J, Nisolle M, Gillet N, Smets M, Bassil S, Casanas-Roux F. Large ovarian endometriomas. Hum Reprod. 1996;11(3):641–646. Sutton CJ, Ewen SP, Jacobs SA, Whitelaw NL. Laser laparoscopic surgery in the treatment of ovarian endometriomas. J Am Assoc Gynecol Laparosc. 1997;4(3):319–323. Muzii L, Bellati F, Bianchi A, et al. Laparoscopic stripping of endometriomas: a randomized trial on different surgical techniques. Part II: Pathological results. Hum Reprod. 2005;20(7):1987–1992. Evers JL, Dunselman GA, Land JA, Bouckaert PX. Management of recurrent endometriosis. In: Couinho E, Spinola P, DeMoura LH, eds. Progress in the Management of Endometriosis. London, UK: Partheon, 1995:291–297. Garry R. The effectiveness of laparoscopic excision of endometriosis. Curr Opin Obstet Gynecol. 2004;16(4):299–303. Laschke MW, Elitzsch A, Vollmar B, Vajkoczy P, Menger MD. Combined inhibition of vascular endothelial growth factor (VEGF), fibroblast growth factor and platelet-derived growth factor, but not inhibition of VEGF alone, effectively suppresses angiogenesis and vessel maturation in endometriotic lesions. Hum Reprod. 2006;21(1):262–268. Laschke MW, Menger MD. In vitro and in vivo approaches to study angiogenesis in the pathophysiology and therapy of endometriosis. Hum Reprod Update. 2007;13(4):331–342. Tan XJ, Lang JH, Liu DY, Shen K, Leng JH, Zhu L. Expression of vascular endothelial growth factor and thrombospondin-l mRNA in patients with endometriosis. Fertil Steril. 2002;78(1):148–153. Gilabert-Estellés J, Ramón LA, EspañaF, et al. Expression of angiogenic factors in endometriosis: its relation to fibrinolytic and metalloproteinase (MMP) systems. Hum Reprod. 2007;22(8):2120–2127. Ramón LA, Braza-Boïls A, Gilabert-Estellés J, et al. microRNAs expression in endometriosis and their relation to angiogenic factors. Hum Reprod. 2011;26(5): 1082–1090. Lanz RB, McKenna NJ, Onate SA, et al. A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex. Cell. 1999;97(1):17–27. Leygue E, Dotzlaw H, Watson PH, Murphy LC. Expression of the steroid receptor RNA activator in human breast tumors. Cancer Res. 1999;59(17):4190–4193. Lanz RB, Chua SS, Barron N, Söder BM, DeMayo F, O’Malley BW. Steroid receptor RNA activator stimulates proliferation as well as apoptosis in vivo. Mol Cell Biol. 2003;23(10):7163–7176. Cooper C, Guo J, Yan Y, et al. Increasing the relative expression of endogenous non-coding Steroid Receptor RNA Activator (SRA) in human breast cancer cells using modified oligonucleotides. Nucleic Acids Res. 2009;37(13):4518–4531. Agoulnik IU, Weigel NL. Coactivator selective regulation of androgen receptor activity. Steroids. 2009;74(8):669–674. Hube F, Guo J, Chooniedass-Kothari S, et al. Alternative splicing of the first intron of the steroid receptor RNA activator (SRA) participates in the generation of coding and noncoding RNA isoforms in breast cancer cell lines. DNA Cell Biol. 2006;25(7):418–428. Kawashima H, Takano H, Sugita S, Takahara Y, Sugimura K, Nakatani T. A novel steroid receptor co-activator protein (SRAP) as an alternative form of steroid receptor RNA-activator gene: expression in prostate cancer cells and enhancement of androgen receptor activity. Biochem J. 2003;369(pt 1):163–171. KurisuT, TanakaT, Ishii J, etal. Expression and function of human steroid receptor RNA activator in prostate cancer cells: role of endogenous hSRA protein in androgen receptor-mediated transcription. Prostate Cancer Prostatic Dis. 2006;9(2):173–178. Chooniedass-Kothari S, Vincett D, Yan Y, et al. The protein encoded by the functional steroid receptor RNA activator is a new modulator of ER alpha transcriptional activity. FEBS Lett. 2010; 584(6): 1174–1180. O’Malley BW, McKenna NJ. Coactivators and corepressors: what’s in a name? Mol Endocrinol. 2008;22(10):2213–2214. Bulun SE. Endometriosis. N Engl J Med. 2009;360(3):268–279. Hyder SM, Nawaz Z, Chiappetta C, Stancel GM. Identification of functional estrogen response elements in the gene coding for the potent angiogenic factor vascular endothelial growth factor. Cancer Res. 2000;60(12):3183–3190. Mueller MD, Vigne JL, Minchenko A, Lebovic DI, Leitman DC, Taylor RN. Regulation of vascular endothelial growth factor (VEGF) gene transcription by estrogen receptors alpha and beta. Proc Natl Acad Sci USA. 2000;97(20): 10972–10977. Attar E, Bulun SE. Aromatase and other steroidogenic genes in endometriosis: translational aspects. Hum Reprod Updat. 2006; 12(1):49–56. American Society for Reproductive Medicine. Revised American Society for Reproductive Medicine classification of endometriosis 1996. Fertil Steril. 1997;67(5):817–821. Schmid-Braz AT, Cavalli LR, Cornélio DA, et al. Comprehensive cytogenetic evaluation of a mature ovarian teratoma case. Cancer Genet Cytogenet. 2002;132(2):165–168. Noyes RW, Hertig AT, Rock J. Dating the endometrial biopsy. Fertil Steril. 1950;1:3–5. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2 (-Delta Delta C (T)) method. Methods. 2001;25(4):402–408. Emberley E, Huang GJ, Hamedani MK, et al. Identification of new human coding steroid receptor RNA activator isoforms. Biochem Biophys Res Commun. 2003;301(2):509–15. Chooniedass-Kothari S, Emberley E, Hamedani MK, et al. The steroid receptor RNA activator is the first functional RNA encoding a protein. FEBS Lett. 2004;566(1–3):43–47. Takehara M, Ueda M, Yamashita Y, Terai Y, Hung YC, Ueki M. Vascular endothelial growth factor A and C gene expression in endometriosis. Hum Pathol. 2004;35(11): 1369–1375. Nisolle M, Donnez J. Peritoneal endometriosis, ovarian endometriosis and adenomyotic nodules of the rectovaginal septum are three different entities. Fert Steril. 1997;68(4):585–596. Borth N, Massier J, Franke C, Sachse K, Saluz HP, Hänel F. Chlamydial protease CT441 interacts with SRAP1 co-activator of estrogen receptor alpha and partially alleviates its co-activation activity. J Steroid Biochem Mol Biol. 2010;119(1–2):89–95. Masuda H, Kalka C, Takahashi T, et al. Estrogen-mediated endothelial progenitor cell biology and kinetics for physiological postnatal vasculogenesis. Circ Res. 2007;101(6):598–606. Masuda H, Matsuzaki Y, Hiratsu E, et al. Stem cell-like properties of the endometrial side population: implication in endometrial regeneration. PLoS One. 2010;5(4):e10387. Hegele-Hartung C, Siebel P, Peters O, et al. Impact of isotypeselective estrogen receptor agonists on ovarian function. Proc Natl Acad Sci USA. 2004;101(14):5129–5134. Gargett CE, Schwab KE, Zillwood RM, Nguyen HPT, Wu D. Isolation and culture of epithelial progenitors and mesenchymal stem cells from human endometrium. Biol Reprod. 2009;80(6): 1136–1145. Chan RWS, Ng EHY, Yeung WSB. Identification of cells with colony-forming activity, self-renewal capacity, and multipotency in ovarian endometriosis. Am J Pathol. 2011;178(6): 2832–2844. Nilbert M, Pejovic T, Mandahl N, Iosif S, Willen H, Mitelman F. Monoclonal origin of endometriotic cysts. Lnt J Gynecol Cancer. 1995;5(1):61–63. Nabeshima H, Murakami T, Yoshinaga K, Sato K, Terada Y, Okamura K. Analysis of the clonality of ectopic glands in peritoneal endometriosis using laser microdissection. Fertil Steril. 2003;80(5):1144–1150. Jiang X, Hitchcock A, Bryan EJ, et al. Microsatellite analysis of endometriosis reveals loss of heterozygosity at candidate ovarian tumor suppressor gene loci. Cancer Res. 1996;56(15):3534–3539. Jimbo H, Hitomi Y, Yoshikawa H, et al. Evidence for monoclonal expansion of epithelial cells in ovarian endometrial cysts. Am J Pathol. 1997;150(4):1173–1178. Jimbo H, Hitomi Y, Yoshikawa H, et al. Clonality analysis of bilateral ovarian endometrial cysts. Fertil Steril. 1999;72(6): 1142–1143. Mayr D, Amann G, Siefert C, Diebold J, Anderegg B. Does endometriosis really have premalignant potential? A clonal analysis of laser-microdissected tissue. FASEB J. 2003;17(6):693–695. Tamura M, Fukaya T, Murakami T, Uehara S, Yajima A. Analysis of clonality in human endometriotic cysts based on evaluation of X chromosome inactivation in archival formalin-fixed, paraffin-embedded tissue. Lab Invest. 1998;78(2):213–218. Wu Y, Basir Z, Kajdacsy-Balla A, et al. Resolution of clonal origins for endometriotic lesions using laser capture microdissection and the human androgen receptor (HUMARA) assay. Fertil Steril. 2003;79(suppl 1):710–717. Cheong Y, Tay P, Luk F, Gan HC, Li TC, Cooke I. Laparoscopic surgery for endometriosis: how often do we need to re-operate? J Obstet Gynaecol. 2008;28(1):82–85. Liu H, Lang J. Is abnormal eutopic endometrium the cause of endometriosis? The role of eutopic endometrium in pathogenesis of endometriosis. Med Sci Monit. 2011;17(4):RA92-RA99. Lucidi RS, Witz CA, Chrisco M, Binkley PA, Shain SA, Schenken RS. A novel in vitro model of the early endometriotic lesion demonstrates that attachment of endometrial cells to mesothelial cells is dependent on the source of endometrial cells. Fertil Steril. 2005;84(1):16–21. Exacoustos C, Zupi E, Amadio A, et al. Recurrence of endometriomas after laparoscopic removal: sonographic and clinical follow-up and indication for second surgery. J Minim Lnvasive Gynecol. 2006;13(4):281–288. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Lin, K., Ma, J., Wu, R. et al. Influence of Ovarian Endometrioma on Expression of Steroid Receptor RNA Activator, Estrogen Receptors, Vascular Endothelial Growth Factor, and Thrombospondin 1 in the Surrounding Ovarian Tissues. Reprod. Sci. 21, 183–189 (2014). https://doi.org/10.1177/1933719113492205 Published: Issue date: DOI: https://doi.org/10.1177/1933719113492205