Top

Archives of Gynecology and Obstetrics

Published in:

01-04-2012 | General Gynecology

Co-expression of bone morphogenetic protein 6 with estrogen receptor a in endometriosis

Authors: Farfaras Athanasios, Nonni Afrodite, Patsouris Effstratios, Kassanos Demetrios

Published in: Archives of Gynecology and Obstetrics | Issue 4/2012

Abstract

Background

Bone morphogenetic protein 6 (BMP-6) has decisive role in controlling multiple organogenetic processes, as well as modulating cell differentiation and proliferation. Considering those pleiotropic effects, we focused on determining expression of that multifunctional growth factor in ectopic endometriotic tissues.

Materials and methods

In this prospective study, 85 consecutive women with endometriosis were included. All patients underwent gynecological operations due to endometriosis associated problems and tissue specimens were collected from ectopic endometriotic lesions. Immunohistochemical staining of paraffin sections for both BMP-6 and estrogen receptors a (ERa) was performed in all 85 cases using an avidin–biotin–peroxidase procedure.

Results

Ectopic endometrium showed intense cytoplastic immunoreactivity to BMP-6 in both epithelium and stroma. In addition, we have demonstrated that BMP-6 expression is highly associated with strong expression of ERa.

Discussion

The availability of BMP-6 in the ectopic endometrium may be at least partly involved in the mechanisms of attachment, survival and expansion of endometriosis. Moreover, the statistically significant correlation in expression of BMP-6 and ERa demonstrated in this study may be associated with the development of rich in estrogen microenvironment, but requires further investigation. In conclusion, this is the first study in our knowledge demonstrating strong expression of BMP-6 in endometriosis.

Vigano P, Parazzini F, Somigliana E, Vercellini P (2004) Endometriosis: epidemiology and aetiological factors. Best Pract Res Clin Obstet Gynaecol 18(2):177–200PubMedCrossRef

Holoch KJ, Lessey BA (2010) Endometriosis and infertility. Clin Obstet Gynecol 53(2):429–438PubMedCrossRef

Sampson JA (1927) Metastatic or embolic endometriosis, due to the menstrual dissemination of endometrial tissue into the venous circulation. Am J Pathol 3(2):93–110 43

Von Recklinghausen F (1896) Adenomyomas and cystadenomas of the wall of the uterus and tube: their origin as remnants of the wolffian body. Wien Klin Wochenschr 8:530

Ridley JH (1981) Coelomic metaplasia. Am J Obstet Gynecol 140(2):233–234PubMed

Cullen T (1920) The distribution of adenomyoma containing uterine mucosa. Arch Surg 1:215–283CrossRef

Javert CT (1949) Pathogenesis of endometriosis based on endometrial homeoplasia, direct extension, exfoliation and implantation, lymphatic and hematogenous metastasis, including five case reports of endometrial tissue in pelvic lymph nodes. Cancer 2(3):399–410PubMedCrossRef

Leyendecker G, Wildt L, Mall G (2009) The pathophysiology of endometriosis and adenomyosis: tissue injury and repair. Arch Gynecol Obstet 280(4):529–538PubMedCrossRef

Harada T, Taniguchi F, Izawa M, Ohama Y, Takenaka Y, Tagashira Y et al (2007) Apoptosis and endometriosis. Front Biosci. 12:3140–3151PubMedCrossRef

10.

Sharpe-Timms KL (2001) Endometrial anomalies in women with endometriosis. Ann N Y Acad Sci 943:131–147PubMedCrossRef

11.

Jones RK, Bulmer JN, Searle RF (1995) Immunohistochemical characterization of proliferation, oestrogen receptor and progesterone receptor expression in endometriosis: comparison of eutopic and ectopic endometrium with normal cycling endometrium. Hum Reprod 10(12):3272–3279PubMed

12.

Matsuzaki S, Fukaya T, Uehara S, Murakami T, Sasano H, Yajima A (2000) Characterization of messenger RNA expression of estrogen receptor-alpha and -beta in patients with ovarian endometriosis. Fertil Steril 73(6):1219–1225PubMedCrossRef

13.

Park SH (2005) Fine tuning and cross-talking of TGF-beta signal by inhibitory Smads. J Biochem Mol Biol 38(1):9–16PubMedCrossRef

14.

Johnson MC, Torres M, Alves A, Bacallao K, Fuentes A, Vega M et al (2005) Augmented cell survival in eutopic endometrium from women with endometriosis: expression of c-myc, TGF-beta1 and bax genes. Reprod Biol Endocrinol 3:45PubMedCrossRef

15.

Chang H, Brown CW, Matzuk MM (2002) Genetic analysis of the mammalian transforming growth factor-beta superfamily. Endocr Rev 23(6):787–823PubMedCrossRef

16.

Darby S, Cross SS, Brown NJ, Hamdy FC, Robson CN (2008) BMP-6 over-expression in prostate cancer is associated with increased Id-1 protein and a more invasive phenotype. J Pathol 214(3):394–404PubMedCrossRef

17.

Ducy P, Karsenty G (2000) The family of bone morphogenetic proteins. Kidney Int 57(6):2207–2214PubMedCrossRef

18.

Jones CM, Lyons KM, Hogan BL (1991) Involvement of Bone Morphogenetic Protein-4 (BMP-4) and Vgr-1 in morphogenesis and neurogenesis in the mouse. Development 111(2):531–542PubMed

19.

American Society for Reproductive Medicine. Revised American Society for Reproductive Medicine classification of endometriosis. Fertil Steril 1997(67.5):817–821

20.

Akiyoshi T, Uchida K, Tateyama S (2004) Expression of bone morphogenetic protein-6 and bone morphogenetic protein receptors in myoepithelial cells of canine mammary gland tumors. Vet Pathol 41(2):154–163PubMedCrossRef

21.

Nonni A, Zagouri F, Sergentanis TN, Lazaris AC, Patsouris ES, Zografos GC (2007) Immunohistochemical expression of estrogen receptors alpha and beta in lobular neoplasia. Virchows Arch 451(5):893–897PubMedCrossRef

22.

Suzuki J, Otsuka F, Inagaki K, Takeda M, Ogura T, Makino H (2004) Novel action of activin and bone morphogenetic protein in regulating aldosterone production by human adrenocortical cells. Endocrinology 145(2):639–649PubMedCrossRef

23.

Dai J, Keller J, Zhang J, Lu Y, Yao Z, Keller ET (2005) Bone morphogenetic protein-6 promotes osteoblastic prostate cancer bone metastases through a dual mechanism. Cancer Res 65(18):8274–8285PubMedCrossRef

24.

Du J, Yang S, Wang Z, Zhai C, Yuan W, Lei R et al (2008) Bone morphogenetic protein 6 inhibit stress-induced breast cancer cells apoptosis via both Smad and p38 pathways. J Cell Biochem 103(5):1584–1597PubMedCrossRef

25.

Kraunz KS, Nelson HH, Liu M, Wiencke JK, Kelsey KT (2005) Interaction between the bone morphogenetic proteins and Ras/MAP-kinase signalling pathways in lung cancer. Br J Cancer 93(8):949–952PubMedCrossRef

26.

Shi J, Yoshino O, Osuga Y, Koga K, Hirota Y, Hirata T et al (2009) Bone morphogenetic protein-6 stimulates gene expression of follicle-stimulating hormone receptor, inhibin/activin beta subunits, and anti-Mullerian hormone in human granulosa cells. Fertil Steril 92(5):1794–1798PubMedCrossRef

27.

Erickson GF, Shimasaki S (2003) The spatiotemporal expression pattern of the bone morphogenetic protein family in rat ovary cell types during the estrous cycle. Reprod Biol Endocrinol 1:9PubMedCrossRef

28.

Juengel JL, Reader KL, Bibby AH, Lun S, Ross I, Haydon LJ et al (2006) The role of bone morphogenetic proteins 2, 4, 6 and 7 during ovarian follicular development in sheep: contrast to rat. Reproduction 131(3):501–513PubMedCrossRef

29.

Campbell BK, Kendall NR, Baird DT (2009) Effect of direct ovarian infusion of bone morphogenetic protein 6 (BMP6) on ovarian function in sheep. Biol Reprod 81(5):1016–1023PubMedCrossRef

30.

Kang Q, Sun MH, Cheng H, Peng Y, Montag AG, Deyrup AT et al (2004) Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery. Gene Ther 11(17):1312–1320PubMedCrossRef

31.

Gitelman SE, Kirk M, Ye JQ, Filvaroff EH, Kahn AJ, Derynck R (1995) Vgr-1/BMP-6 induces osteoblastic differentiation of pluripotential mesenchymal cells. Cell Growth Differ 6(7):827–836PubMed

32.

Giretti MS, Fu XD, De Rosa G, Sarotto I, Baldacci C, Garibaldi S et al (2008) Extra-nuclear signalling of estrogen receptor to breast cancer cytoskeletal remodelling, migration and invasion. PLoS One 3(5):e2238PubMedCrossRef

33.

Rickard DJ, Hofbauer LC, Bonde SK, Gori F, Spelsberg TC, Riggs BL (1998) Bone morphogenetic protein-6 production in human osteoblastic cell lines. Selective regulation by estrogen. J Clin Invest 101(2):413–422PubMedCrossRef

34.

Simic P, Culej JB, Orlic I, Grgurevic L, Draca N, Spaventi R et al (2006) Systemically administered bone morphogenetic protein-6 restores bone in aged ovariectomized rats by increasing bone formation and suppressing bone resorption. J Biol Chem 281(35):25509–25521PubMedCrossRef

35.

Martinovic S, Borovecki F, Miljavac V, Kisic V, Maticic D, Francetic I et al (2006) Requirement of a bone morphogenetic protein for the maintenance and stimulation of osteoblast differentiation. Arch Histol Cytol 69(1):23–36PubMedCrossRef

36.

Zhang M, Yan JD, Zhang L, Wang Q, Lu SJ, Zhang J et al (2005) Activation of bone morphogenetic protein-6 gene transcription in MCF-7 cells by estrogen. Chin Med J (Engl) 118(19):1629–1636

37.

Attar E, Bulun SE (2006) Aromatase and other steroidogenic genes in endometriosis: translational aspects. Hum Reprod Update 12(1):49–56PubMedCrossRef

38.

Frasor J, Danes JM, Komm B, Chang KC, Lyttle CR, Katzenellenbogen BS (2003) Profiling of estrogen up- and down-regulated gene expression in human breast cancer cells: insights into gene networks and pathways underlying estrogenic control of proliferation and cell phenotype. Endocrinology 144(10):4562–4574PubMedCrossRef

39.

Gazvani R, Templeton A (2002) Peritoneal environment, cytokines and angiogenesis in the pathophysiology of endometriosis. Reproduction 123(2):217–226PubMedCrossRef

40.

Hagen M, Fagan K, Steudel W, Carr M, Lane K, Rodman DM et al (2007) Interaction of interleukin-6 and the BMP pathway in pulmonary smooth muscle. Am J Physiol Lung Cell Mol Physiol 292(6):L1473–L1479PubMedCrossRef

41.

Grasser WA, Orlic I, Borovecki F, Riccardi KA, Simic P, Vukicevic S et al (2007) BMP-6 exerts its osteoinductive effect through activation of IGF-I and EGF pathways. Int Orthop 31(6):759–765PubMedCrossRef

42.

Mukai T, Otsuka F, Otani H, Yamashita M, Takasugi K, Inagaki K et al (2007) TNF-alpha inhibits BMP-induced osteoblast differentiation through activating SAPK/JNK signaling. Biochem Biophys Res Commun 356(4):1004–1010PubMedCrossRef

43.

Richter ON, Dorn C, Rosing B, Flaskamp C, Ulrich U (2005) Tumor necrosis factor alpha secretion by peritoneal macrophages in patients with endometriosis. Arch Gynecol Obstet 271(2):143–147PubMedCrossRef

44.

van der Linden PJ, de Goeij AF, Dunselman GA, van der Linden EP, Ramaekers FC, Evers JL (1994) Expression of integrins and E-cadherin in cells from menstrual effluent, endometrium, peritoneal fluid, peritoneum, and endometriosis. Fertil Steril 61(1):85–90PubMed

45.

Ceyhan ST, Onguru O, Baser I, Gunhan O (2008) Expression of cyclooxygenase-2 and vascular endothelial growth factor in ovarian endometriotic cysts and their relationship with angiogenesis. Fertil Steril 90(4):988–993PubMedCrossRef

46.

Starzinski-Powitz A, Gaetje R, Zeitvogel A, Kotzian S, Handrow-Metzmacher H, Herrmann G et al (1998) Tracing cellular and molecular mechanisms involved in endometriosis. Hum Reprod Update 4(5):724–729PubMedCrossRef

47.

Kao AP, Wang KH, Chang CC, Lee JN, Long CY, Chen HS et al (2010) Comparative study of human eutopic and ectopic endometrial mesenchymal stem cells and the development of an in vivo endometriotic invasion model. Fertil Steril Nov 1

48.

Valdimarsdottir G, Goumans MJ, Rosendahl A, Brugman M, Itoh S, Lebrin F et al (2002) Stimulation of Id1 expression by bone morphogenetic protein is sufficient and necessary for bone morphogenetic protein-induced activation of endothelial cells. Circulation 106(17):2263–2270PubMedCrossRef

49.

Ren R, Charles PC, Zhang C, Wu Y, Wang H, Patterson C (2007) Gene expression profiles identify a role for cyclooxygenase 2-dependent prostanoid generation in BMP6-induced angiogenic responses. Blood 109(7):2847–2853PubMed

50.

Erickson GF, Fuqua L, Shimasaki S (2004) Analysis of spatial and temporal expression patterns of bone morphogenetic protein family members in the rat uterus over the estrous cycle. J Endocrinol 182(2):203–217PubMedCrossRef

51.

Koninckx PR, Ide P, Vandenbroucke W, Brosens IA (1980) New aspects of the pathophysiology of endometriosis and associated infertility. J Reprod Med 24(6):257–260PubMed

52.

Ridley JH, Edwards IK (1958) Experimental endometriosis in the human. Am J Obstet Gynecol 76(4):783–789 discussion 9−90PubMed

Title: Co-expression of bone morphogenetic protein 6 with estrogen receptor a in endometriosis
Authors: Farfaras Athanasios
Nonni Afrodite
Patsouris Effstratios
Kassanos Demetrios
Publication date: 01-04-2012
Publisher: Springer-Verlag
Published in: Archives of Gynecology and Obstetrics / Issue 4/2012
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-011-2082-8

At a glance: The STEP trials

Springer Medicine

Co-expression of bone morphogenetic protein 6 with estrogen receptor a in endometriosis

Abstract

Background

Materials and methods

Results

Discussion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Materials and methods

Results

Discussion

Please log in to get access to this content

Other articles of this Issue 4/2012

Endometrial adenocarcinoma with osteoclastic giant cells in stroma: a case report and review of literature

Maternal and neonatal outcomes of spontaneously conceived pregnancies in mothers over 45 years: a review of the literature

Primary Ewing’s sarcoma/primitive neuroectodermal tumor of the vagina in a 54-year-old woman: a case report

Risk factors and perinatal outcome of pregnancies complicated with cephalopelvic disproportion: a population-based study

Selective and non-selective intrauterine growth restriction in twin pregnancies: high-risk factors and perinatal outcome

Vaginal hysterectomy and multimodal anaesthesia with bipolar vessel sailing (Biclamp® forceps) versus conventional suture technique: quality results’ analysis