Skip to main content
SpringerLink
Log in

Surgical Removal of Endometrioma Decreases the NF-kB1 (p50/105) and NF-kB p65 (Rel A) Expression in the Eutopic Endometrium During the Implantation Window

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

We aimed to investigate whether the surgical removal of endometrioma alters the nuclear factor-kappa B1 (NF-kB1; p50/105) and NF-kB p65 (Rel A) expression in the eutopic endometrium of infertile women with endometrioma before and after laparoscopic removal of the ovarian endometrioma during the mid-secretory phase. Infertile women with endometrioma (n = 15) were enrolled. Infertile patients with nonendometriotic ovarian cyst (n = 10) and healthy fertile women (n = 10) were recruited as controls. Endometrial samples were obtained before and 3 months after the laparoscopic cystectomy. The NF-kB1 (p50/105) levels were analyzed by enzyme-linked immunosorbent assay (ELISA) in the endometrium of all groups before and after laparoscopic ovarian cystectomy during implantation window. Expression of NF-kB1 (p50/105) in eutopic endometrium was significantly higher in infertile women with endometrioma compared to nonendometriotic cyst and fertile controls (P < .05). Laparoscopic cystectomy resulted in a significant decrease in NF-kB1 expression in women with endometrioma. The NF-kB p65 (Rel A) immunoreactivity of eutopic endometrium decreased significantly subsequent to the surgical removal of the endometrioma. In conclusion, increased endometrial NF-kB expression may contribute to endometriosis-associated infertility.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Houston DE. Evidence for the risk of pelvic endometriosis by age, race and socioeconomic status. Epidemiol Rev. 1984;6:167–191.

    Article  CAS  PubMed  Google Scholar 

  2. Cramer DW. Epidemiology of endometriosis in adolescents. In: Wilson EA, ed. Endometriosis. New York, NY: Alan Liss, 1987:5–8.

  3. Strathy JH, Molgaard CA, Coulam CB, Melton LJ III. Endometriosis and infertility: a laparoscopic study of endometriosis among fertile and infertile women. Fertil Steril. 1982;38(6): 667–672.

    Article  CAS  PubMed  Google Scholar 

  4. Giudice LC, Kao LC. Endometriosis. Lancet. 2004;364(9447): 1789–1799.

    Article  PubMed  Google Scholar 

  5. Tummon IS, Maclin VM, Radwanska E, Binor Z, Dmowski WP. Occult ovulatory dysfunction in women with minimal endometriosis or unexplained infertility. Fertil Steril. 1988; 50(5):716–720.

    Article  CAS  PubMed  Google Scholar 

  6. Simón C, Gutiérrez A, Vidal A, et al. Outcome of patients with endometriosis in assisted reproduction: results from in-vitro fertilization and oocyte donation. Hum Reprod. 1994;9(4):725–729.

    Article  PubMed  Google Scholar 

  7. Ulukus M, Cakmak H, Arici A. The role of endometrium in endometriosis. J Soc Gynecol Investig. 2006;13(7):467–476.

    Article  CAS  PubMed  Google Scholar 

  8. Giudice LC, Telles TL, Lobo S, Kao L. The molecular basis for implantation failure in endometriosis: on the road to discovery. Ann N Y Acad Sci. 2002;955:252–264.

    Article  CAS  PubMed  Google Scholar 

  9. Somigliana E, Vercellini P, Viganó P, Ragni G, Crosignani PG. Should endometriomas be treated before IVF-ICSI cycles? Hum Reprod Update. 2006;12(1):57–64.

    Article  PubMed  Google Scholar 

  10. Demirol A, Guven S, Baykal C, Gurgan T. Effect of endometrioma cystectomy on IVF outcome: a prospective randomized study. Reprod Biomed Online. 2006;12(5):639–643.

    Article  PubMed  Google Scholar 

  11. Var T, Batioglu S, Tonguc E, Kahyaoglu I. The effect of laparoscopic ovarian cystectomy versus coagulation in bilateral endometriomas on ovarian reserve as determined by antral follicle count and ovarian volume: a prospective randomized study. Fertil Steril. 2011;95(7):2247–2250.

    Article  PubMed  Google Scholar 

  12. Loo TC, Lin MY, Chen SH, et al. Endometrioma undergoing laparoscopic ovarian cystectomy: its influence on the outcome of in vitro fertilization and embryo transfer (IVF-ET). J Assist Reprod Genet. 2005;22(9–10):329–333.

    Article  PubMed  Google Scholar 

  13. Alborzi S, Momtahan M, Parsanezhad ME, Dehbashi S, Zolghadri J, Alborzi S. A prospective, randomized study comparing laparoscopic ovarian cystectomy versus fenestration and coagulation in patients with endometriomas. Fertil Steril. 2004;82(6):1633–1637.

    Article  PubMed  Google Scholar 

  14. Celik O, Hascalik S, Elter K, Tagluk ME, Gurates B, Aydin NE. Combating endometriosis by blocking proteasome and nuclear factor-kappaB pathways. Hum Reprod. 2008;23(11):2458–2465.

    Article  CAS  PubMed  Google Scholar 

  15. Lu Y, Sun Q, Zheng Y, Liu X, Geng JG, Guo SW. The role of nuclear factor-kappa-B p50 subunit in the development of endometriosis. Front Biosci (Elite Ed). 2011;3:591–603.

    Google Scholar 

  16. Shen F, Wang Y, Lu Y, Yuan L, Liu X, Guo SW. Immunoreactivity of progesterone receptor isoform B and nuclear factor kappa-B as biomarkers for recurrence of ovarian endometriomas. Am J Obstet Gynecol. 2008;199(5):486.e1–486.e10.

    Article  CAS  Google Scholar 

  17. Novak U, Cocks BG, Hamilton JA. A labile repressor acts through the NFkB-like binding sites of the human urokinase gene. Nucleic Acids Res. 1991;19(12):3389–3393.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Aggarwal BB. Nuclear factor-kB: the enemy within. Cancer Cell. 2004;6(3):203–208.

    Article  CAS  PubMed  Google Scholar 

  19. Laird SM, Tuckerman EM, Cork BA, Li TC. Expression of nuclear factor k B in human endometrium; role in the control of interleukin 6 and leukaemia inhibitory factor production. Mol Hum Reprod. 2000;6(1):34–40.

    Article  CAS  PubMed  Google Scholar 

  20. King AE, Critchley H, Kelly RW. The NF-kB pathway in human endometrium and first trimester decidua. Mol Hum Reprod. 2001; 7(2):175–183.

  21. González-Ramos R, Rocco J, Rojas C, et al. Physiologic activation of nuclear factor kappa-B in the endometrium during the menstrual cycle is altered in endometriosis patients. Fertil Steril. 2012;97(3):645–651.

    Article  PubMed  CAS  Google Scholar 

  22. Han S, Sidell N. RU486-induced growth inhibition of human endometrial cells involves the nuclear factor-kB signaling pathway. J Clin Endocrinol Metab. 2003;88(2):713–719.

    Article  CAS  PubMed  Google Scholar 

  23. Beinke S, Ley SC. Functions of NF-kappaB1 and NF-kappaB2 in immune cell biology. Biochem J. 2004;382(pt 2):393–409.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chen LF, Greene WC. Shaping the nuclear action of NF-kappaB. Nat Rev Mol Cell Biol. 2004;5(5):392–401.

    Article  CAS  PubMed  Google Scholar 

  25. Pahl HL. Activators and target genes of Rel/NF kappaB transcription factors. Oncogene. 1999;18(49):6853–6866.

    Article  CAS  PubMed  Google Scholar 

  26. Renard P, Raes M. The proinflammatory transcription factor NFkappaB: a potential target for novel therapeutical strategies. Cell Biol Toxicol. 1999;15(6):341–344.

    Article  CAS  PubMed  Google Scholar 

  27. Karin M, Yamamoto Y, Wang QM. The IKK NF-kB system: a treasure trove for drug development. Nat Rev Drug Discov. 2004;3(1):17–26.

    Article  CAS  PubMed  Google Scholar 

  28. Hoffmann A, Baltimore D. Circuitry of nuclear factor kB signaling. Immunol Rev. 2006;210:171–186.

    Article  PubMed  Google Scholar 

  29. Noyes RW, Hertig AT, Rock J. Dating the endometrial biopsy. Am J Obstet Gynecol. 1975;122(2):262–263.

    Article  CAS  PubMed  Google Scholar 

  30. Ordi J, Creus M, Ferrer B, et al. Midluteal endometrial biopsy and alphavbeta3 integrin expression in the evaluation of the endometrium in infertility: implications for fecundity. Int J Gynecol Pathol. 2002;21(3):231–238.

    Article  PubMed  Google Scholar 

  31. Creus M, Ordi J, Fábregues F, et al. alphavbeta3 integrin expression and pinopod formation in normal and out-of-phase endometria of fertile and infertile women. Hum Reprod. 2002;17(9): 2279–2286.

    Article  CAS  PubMed  Google Scholar 

  32. Budwit-Novotny DA, McCarty KS, Cox EB, et al. Immunohistochemical analyses of estrogen receptor in endometrial adenocarcinoma using a monoclonal antibody. Cancer Res. 1986;46(10): 5419–5425.

    CAS  PubMed  Google Scholar 

  33. Lessey BA, Castelbaum AJ, Sawin SW, et al. Aberrant integrin expression in the endometrium of women with endometriosis. J Clin Endocrinol Metab. 1994;79(2):643–649.

    CAS  PubMed  Google Scholar 

  34. Ponce C, Torres M, Galleguillos C, et al. Nuclear factor kappaB pathway and interleukin-6 are affected in eutopic endometrium of women with endometriosis. Reproduction. 2009;137(4): 727–737.

    Article  CAS  PubMed  Google Scholar 

  35. McKay LI, Cidlowski JA. Cross-talk between nuclear factor-kappa B and the steroid hormone receptors: mechanisms of mutual antagonism. Mol Endocrinol. 1998;12(1):45–56.

    Article  CAS  PubMed  Google Scholar 

  36. Metzger DA, Olive DL, Haney AF. Limited hormonal responsiveness of ectopic endometrium: histologic correlation with intrauterine endometrium. Hum Pathol. 1988;19(12): 1417–1424.

    Article  CAS  PubMed  Google Scholar 

  37. Burney RO, Hamilton AE, Aghajanova L, et al. MicroRNA expression profiling of eutopic secretory endometrium in women with versus without endometriosis. Mol Hum Reprod. 2009; 15(10):625–631.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Achache H, Revel A. Endometrial receptivity markers, the journey to successful embryo implantation. Hum Reprod Update. 2006;12(6):731–746.

    Article  PubMed  Google Scholar 

  39. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Taylor HS, Igarashi P, Olive DL, Arici A. Sex steroids mediate HOXA11 expression in the human peri-implantation endometrium. J Clin Endocrinol Metab. 1999;84(3):1129–1135.

    CAS  PubMed  Google Scholar 

  41. Cakmak H, Taylor HS. Molecular mechanisms of treatment resistance in endometriosis: the role of progesterone-hox gene interactions. Semin Reprod Med.2010;28(1):69–74.

    Article  CAS  Google Scholar 

  42. 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.

    Article  CAS  PubMed  Google Scholar 

  43. 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.

    CAS  PubMed  Google Scholar 

  44. 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Martin M, Herceg Z. From hepatitis to hepatocellular carcinoma: a proposed model for cross-talk between inflammation and epigenetic mechanisms. Genome Med. 2012;4(1):8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Hartnett L, Egan LJ. Inflammation, DNA methylation and colitis-associated cancer. Carcinogenesis. 2012;33(4):723–731.

    Article  CAS  PubMed  Google Scholar 

  47. Lynch VJ, Brayer K, Gellersen B, Wagner GP, HoxA-11 and FOXO1A cooperate to regulate decidual prolactin expression: towards interferring the core transcriptional regulators of decidual genes. PLoS ONE, 2009;4:e6845.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Ben-Jonathan N, Mershon JL, Allen DL, Steinmetz RW. Extrapituitary prolactin: distribution, regulation, functions, and clinical aspects. Endocr Rev. 1996;17(6):639–669.

    CAS  PubMed  Google Scholar 

  49. Jabbour HN, Critchley HO. Potential roles of decidual prolactin in early pregnancy. Reproduction. 2001;121(2):197–205.

    Article  CAS  PubMed  Google Scholar 

  50. Strandell A, Lindhard A, Waldenström U, Thorburn J. Hydrosalpinx and IVF outcome: cumulative results after salpingectomy in a randomized controlled trial. Hum Reprod. 2001;16(11):2403–2410.

    Article  CAS  PubMed  Google Scholar 

  51. Johnson NP, Mak W, Sowter MC. Surgical treatment for tubal disease in women due to undergo in vitro fertilisation. Cochrane Database Syst Rev. 2004;(3):CD002125.

  52. Cermik D, Selam B, Taylor HS. Regulation of HOXA 10 expression by testosterone in vitro and in the endometrium of patients with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003;88(1):238–243.

    Article  CAS  PubMed  Google Scholar 

  53. Rackow BW, Taylor HS. Submucosal uterine leiomyomas have a global effect on molecular determinants of endometrial receptivity. Fertil Steril. 2010;93(6):2027–2034.

    Article  CAS  PubMed  Google Scholar 

  54. Klemmt PA, Carver JG, Kennedy SH, Koninckx PR, Mardon HJ. Stromal cells from endometriotic lesions and endometrium from women with endometriosis have reduced decidualization capacity. Fertil Steril. 2006;85(3):564–572.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Vitiello D, Kodaman PH, Taylor HS. HOX genes in implantation. Semin Reprod Med. 2007;25(6):431–436.

    Article  CAS  PubMed  Google Scholar 

  56. Daftary GS, Kayisli U, Seli E, Bukulmez O, Arici A, Taylor HS. Salpingectomy increases peri implantation endometrial HOXA10 expression in women with hydrosalpinx. Fertil Steril. 2007;87(2): 367–372.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetric and Gynecology, Inonu University, School of Medicine, 44069, Malatya, Turkey

    Onder Celik MD, Ebru Celik MD, Ilgin Turkcuoglu MD, Ercan Yilmaz MD, Yavuz Simsek MD & Abdullah Karaer MD

  2. Department of Physiology, Firat University, School of Medicine, Elazig, Turkey

    Mustafa Ulas

  3. Department of Biochemistry, Malatya State Hospital, Malatya, Turkey

    Nilufer Celik

  4. Department of Pathology, Inonu University, School of Medicine, Malatya, Turkey

    Nasuhi Engin Aydin MD

  5. Department of Microbiology, Inonu University, School of Medicine, Malatya, Turkey

    Ibrahim Ozerol MD

  6. Department of Obstetric and Gynecology, Acibadem University, School of Medicine, Istanbul, Turkey

    Cihat Unlu MD

Authors
  1. Onder Celik MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ebru Celik MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ilgin Turkcuoglu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ercan Yilmaz MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mustafa Ulas
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yavuz Simsek MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Abdullah Karaer MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nilufer Celik
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Nasuhi Engin Aydin MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ibrahim Ozerol MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Cihat Unlu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Onder Celik MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Celik, O., Celik, E., Turkcuoglu, I. et al. Surgical Removal of Endometrioma Decreases the NF-kB1 (p50/105) and NF-kB p65 (Rel A) Expression in the Eutopic Endometrium During the Implantation Window. Reprod. Sci. 20, 762–770 (2013). https://doi.org/10.1177/1933719112466307

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719112466307

Keywords

Search

Navigation