Artículo

Gonzalez, C.R.; Matzkin, M.E.; Frungieri, M.B.; Terradas, C.; Ponzio, R.; Puigdomenech, E.; Levalle, O.; Calandra, R.S.; Gonzalez-Calvar, S.I. "Expression of the TGF-beta1 system in human testicular pathologies" (2010) Reproductive Biology and Endocrinology. 8
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Abstract:

Background: In non-obstructive azoospermia, histological patterns of Sertoli cell-only Syndrome (SCO) and hypospermatogenesis (H) are commonly found. In these pathologies, Leydig cell hyperplasia (LCH) is detected in some patients. Since TGF-β1 is involved in cellular proliferation/development, the aim of this work was to analyze the expression of TGF-β1, its receptors TGFBRII, TGFBRI (ALK-1 and ALK-5), and the co-receptor endoglin in human biopsies from patients with idiopathic infertility.Methods: Specific immunostaining of TGF-β1, its receptors TGFBRII, TGFBRI (ALK-1 and ALK-5), co-receptor endoglin and Smads proteins, were carried out in testicular biopsies from normal and infertile men with SCO or H. Gene expression of TGF-β1 system were made in biopsies from infertile patients with semi-quantitative and quantitative PCR.Results: Immunohistochemical studies revealed that TGF-β1 and its specific receptors are present in Leydig cells in biopsies from normal tissue or patients with SCO or H with or without LCH. Smad proteins, which are involved in TGF-β1 signaling, are also detected in both their phosphorylated (activated) and dephosphorylated form in all samples TGF-β1, ALK-1 and endoglin gene expression are stronger in human biopsies with LCH than in those with SCO or H. Neither TGFBRII nor ALK-5 gene expression showed significant differences between pathologies. A significant correlation between ALK-1 and endoglin expression was observed.Conclusions: In conclusion, the high levels of mRNA and protein expression of the TGF-β1 system in patients with LCH, particularly ALK1 and its correlation with endoglin, suggest that these proteins acting in concert might be, at least in part, committed actors in the Leydig cell hyperplasia. © 2010 Gonzalez et al; licensee BioMed Central Ltd.

Registro:

Documento: Artículo
Título:Expression of the TGF-beta1 system in human testicular pathologies
Autor:Gonzalez, C.R.; Matzkin, M.E.; Frungieri, M.B.; Terradas, C.; Ponzio, R.; Puigdomenech, E.; Levalle, O.; Calandra, R.S.; Gonzalez-Calvar, S.I.
Filiación:Instituto de Biología y Medicina Experimental (CONICET), Vuelta de Obligado 2490, (1428) Buenos Aires, Argentina
División Endocrinología, Hospital Durand, Av. Díaz Velez 5044, (1405) Buenos Aires, Argentina
Instituto Medico PREFER, Calle 995 N 2348, San Martín (6000), Argentina
Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155 (1121), Buenos Aires, Argentina
Palabras clave:endoglin; messenger RNA; Smad protein; Smad1 protein; Smad2 protein; Smad3 protein; Smad5 protein; transforming growth factor beta receptor 1; transforming growth factor beta receptor 2; transforming growth factor beta1; activin receptor 2; ACVRL1 protein, human; cell surface receptor; ENG protein, human; leukocyte antigen; messenger RNA; protein serine threonine kinase; Smad protein; TGF beta type I receptor; TGF-beta type I receptor; transforming growth factor beta receptor; transforming growth factor beta type II receptor; transforming growth factor beta1; transforming growth factor-beta type II receptor; adult; article; clinical article; gene expression; human; human tissue; hypospermatogenesis; immunopathology; infertility; Leydig cell; male; nucleotide sequence; polymerase chain reaction; Sertoli cell only syndrome; testis disease; biosynthesis; hyperplasia; male infertility; metabolism; middle aged; pathology; testis; Activin Receptors, Type II; Adult; Antigens, CD; Humans; Hyperplasia; Infertility, Male; Leydig Cells; Male; Middle Aged; Protein-Serine-Threonine Kinases; Receptors, Cell Surface; Receptors, Transforming Growth Factor beta; RNA, Messenger; Sertoli Cell-Only Syndrome; Smad Proteins; Testicular Diseases; Testis; Transforming Growth Factor beta1
Año:2010
Volumen:8
DOI: http://dx.doi.org/10.1186/1477-7827-8-148
Título revista:Reproductive Biology and Endocrinology
Título revista abreviado:Reprod. Biol. Endocrinol.
ISSN:14777827
CAS:Smad protein, 62395-38-4; Smad1 protein, 444952-89-0; Smad2 protein, 253862-89-4; Smad3 protein, 237417-78-6, 237417-96-8, 237418-00-7; Smad5 protein, 193228-56-7; ACVRL1 protein, human, 2.7.11.30; Activin Receptors, Type II, 2.7.11.30; Antigens, CD; ENG protein, human; Protein-Serine-Threonine Kinases, 2.7.11.1; RNA, Messenger; Receptors, Cell Surface; Receptors, Transforming Growth Factor beta; Smad Proteins; TGF-beta type I receptor, 2.7.1.11; Transforming Growth Factor beta1; transforming growth factor-beta type II receptor, 2.7.11.30
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14777827_v8_n_p_Gonzalez

Referencias:

  • Anniballo, R., Ubaldi, F., Cobellis, L., Sorrentino, M., Rienzi, L., Greco, E., Tesarik, J., Criteria predicting the absence of spermatozoa in the Sertoli cell-only can be use to improve success of sperm retrieval (2000) Human Reprod, 15, pp. 2269-2277
  • Colecchia, M., Nistal, M., Gonzalez-Peramato, P., Carmignani, L., Salvioni, R., Nicolai, N., Regadera, J., Leydig cell Tumor and hyperplasia. A review (2007) Anal Quan Cytol Histol, 29, pp. 1-9
  • Clegg, E.D., Cook, J.C., Chapin, R.E., Foster, P.M., Daston, G.P., Leydig cell hyperplasia and adenoma formation: Mechanisms and relevance to humans (1997) Reprod Toxicol, 11, pp. 107-121. , 10.1016/S0890-6238(96)00203-1, 9138629
  • Ge, R.S., Hardy, M.P., Decreased cyclin A2 and increased cyclin G1 levels coincide with loss of proliferative capacity in rat Leydig cells during pubertal development (1997) Endocrinology, 138, pp. 3719-3726. , 10.1210/en.138.9.3719, 9275057
  • Gould, M.L., Hurst, P.R., Nicholson, H.D., The effects of oestrogen receptors alpha and beta on testicular cell number and steroidogenesis in mice (2007) Reproduction, 134, pp. 271-279. , 10.1530/REP-07-0025, 17660237
  • Chandrashekar, V., Bartke, A., Growth factors in Leydig cell Function (2007) Contemporary Endocrinology: The Leydig cell in Health and Disease, pp. 263-277. , Totowa. N.J, Humana Press Inc, Payne AH, Hardy MP
  • Saez, J.M., Leydig cells: endocrine, paracrine and autocrine regulation (2004) Endocrine Rev, 15, pp. 574-609
  • Khan, S.A., Mirsafian, M., Howdeshell, K., Dorrington, J.H., Transforming growth factor-β inhibits DNA synthesis in immature rat Leydig cells in vitro (1999) Mol Cell Endocrinol, 148, pp. 21-28. , 10.1016/S0303-7207(98)00244-5, 10221767
  • Lui, W.Y., Lee, W.M., Cheng, C.Y., TGF-betas: their role in testicular function and Sertoli cell tight junction dynamics (2003) Int J Androl, 26, pp. 147-160. , 10.1046/j.1365-2605.2003.00410.x, 12755993
  • Sanderson, N., Factor, V., Nagy, P., Kopp, J., Kondaiah, P., Wakefield, L., Roberts, A.B., Thorgeirsson, S.S., Hepatic expression of mature transforming growth factor beta 1 in transgenic mice results in multiple tissue lesions (1995) Proc Natl Acad Sci USA, 92, pp. 2572-2576. , 10.1073/pnas.92.7.2572, 42260, 7708687
  • Teerds, K.J., Dorrington, J.H., Localization of transforming growth factor beta1 and beta2 during testicular development in the rat (1993) Biol Reprod, 48, pp. 40-45. , 10.1095/biolreprod48.1.40, 8418916
  • Massagué, J., Wotton, D., Transcriptional control by TGF-β/Smad signaling system (2000) EMBO J, 19, pp. 1745-1754. , 10.1093/emboj/19.8.1745, 302010, 10775259
  • Itman, C., Mendis, S., Barakat, B., Loveland, K.L., Focus on TGF-β signaling. All in the family: TGF-β family action in testis development (2006) Reproduction, 132, pp. 233-246. , 10.1530/rep.1.01075, 16885532
  • Gautier, C., Levacher, C., Saez, J.M., Habert, R., Transforming growth factor beta1 inhibits steroidogenesis in dispersed fetal testicular cells in culture (1997) Mol Cell Endocrinol, 131, pp. 21-30. , 10.1016/S0303-7207(97)00087-7, 9256360
  • Gnessi, L., Fabbri, A., Spera, G., Gonadal peptides as mediators of development and functional control of the testis: an integrated system with hormones and local environment (1997) Endocr Rev, 18, pp. 541-609. , 10.1210/er.18.4.541, 9267764
  • Narula, A., Kilen, S.K., Ma, E., Kroeger, J., Goldberg, E., Woodruff, T.K., Smad4 overexpression causes germ cell ablation and Leydig cell hyperplasia in transgenic mice (2002) Am J Pathol, 161, pp. 1723-1734. , 1850786, 12414519
  • Ingman, W.V., Robertson, S.A., Defining the actions of transforming growth factor beta in reproduction (2002) BioEssays, 24, pp. 904-914. , 10.1002/bies.10155, 12325123
  • Lutz, M., Knaus, P., Integration of the TGF-β pathway into the cellular signalling network (2002) Cell Signalling, 14, pp. 977-988. , 10.1016/S0898-6568(02)00058-X, 12359303
  • Oh, S.P., Seki, T., Goss, K.A., Imamura, T., Yi, Y., Donahoe, P.K., Li, L., Li, E., Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis (2000) Proc Natl Acad Sci USA, 97, pp. 2626-2631. , 10.1073/pnas.97.6.2626, 15979, 10716993
  • Lebrin, F., Goumans, M.J., Jonker, L., Carvalho, R.L.C., Valdimarsdottir, G., Thorikay, M., Mummery, C., ten Dijke, P., Endoglin promotes endothelial cell proliferation and TGF-β/ALK1 signal transduction (2004) EMBO J, 23, pp. 4018-4028. , 10.1038/sj.emboj.7600386, 524335, 15385967
  • Dobashi, M., Fujisawa, M., Yamasaki, T., Okada I. Kamido, S., Distribution of intracellular and extracellular expression of transforming growth factor-b1 (TGF-β1) in human testis and their association with spermatogenesis (2002) Asian J Androl, 4, pp. 105-109
  • Zhang, Y.Q., He, X.Z., Zhang, J.S., Wang, R.A., Zhou, J., Xu, R.J., Stage-specific localization of transforming growth factor β1 and β3 and their receptors during spermatogenesis in men (2004) Asian J Androl, 6, pp. 105-109
  • McLachlan, R.I., Rajpert-De Meyts, E., Hoei-Hansen, C.E., de Kretser, D.M., Skakkebaek, N.E., Histological evaluation of the human testis-approaches to optimizing the clinical value of the assessment (2007) Human Reprod, 22, pp. 2-16
  • Silber, S.J., Nagy, Z., Devroey, P., Tournaye, H., Van Steirteghem, A.C., Distribution of spermatogenesis in the testicles of azoospermic men: the presence or absence of spermatids in the testes of men with germinal failure (1997) Human Reprod, 12, pp. 2422-2428
  • Silber, S.J., Rodriguez-Rigau, L.J., Quantitative analysis of testicle biopsy: determination of partial obstruction and prediction of sperm count after surgery for obstruction (1981) Fertil Steril, 36, pp. 480-485
  • Holm, M., Rajpert-De Meyts, E., Andersson, A.-M., Skakkebæk, N.E., Leydig cell micronodules are a common finding in testicular biopsies from men with impaired spermatogenesis and are associated with decreased testosterone/LH ratio (2003) J Pathol, 199, pp. 378-386. , 10.1002/path.1309, 12579540
  • Pfaffl, M.W., A new mathematical model for relative quantification in real-time RT-PCR (2001) Nucleic Acids Res, 29, pp. e45. , 10.1093/nar/29.9.e45, 55695, 11328886
  • Carucci, L.R., Tirkes, A.T., Pretorius, E.S., Genega, E.M., Weinstein, S.P., Case report: Testicular Leydig's cells hyperplasia: MR imaging and sonographic findings (2003) Am J Roentgenol, 180, pp. 501-503
  • Bettocchi, C., Parkinson, M.C., Ralph, D.J., Pryor, J.P., Clinical aspects associated with Sertoli-cell-only histology (1998) Br J Urol, 82, pp. 534-537
  • Konrad, L., Keilani, M.M., Laible, L., Nottelmann, U., Hofman, R., Effect of TGF-betas and specific antagonist on apoptosis of immature rat germ cells in vitro (2006) Apoptosis, 11, pp. 739-748. , 10.1007/s10495-006-5542-z, 16532270
  • Suszko, M., Woodruff, T.K., Cell-specificity of transforming growth factor-b-response is dictated by receptor bioavailability (2006) J Mol Endocr, 36, pp. 591-600
  • Razani, B., Zhang, X.L., Bitzer, M., von Gersdorff, G., Bottinger, E.P., Lisanti, M.P., Caveolin-1 regulates transforming growth factor (TGF)-beta/SMAD signaling through an interaction with the TGF-beta type I receptor (2001) J Biol Chem, 276, pp. 6727-6738. , 10.1074/jbc.M008340200, 11102446
  • Lu, Z., Murray, J.T., Luo, W., Li, H., Wu, X., Xu, H., Backer, J.M., Chen, Y.G., Transforming growth factor beta activates Smad2 in the absence of receptor endocytosis (2002) J Biol Chem, 277, pp. 29363-29368. , 10.1074/jbc.M203495200, 12034739
  • Piek, E., Heldin, C.H., ten Dijke, P., Specificity, diversity and regulation in TGF-β superfamily signaling (1999) FASEB J, 13, pp. 2105-2124
  • Shi, Y., Massagué, J., Mechanism of TGF-β signalling from cell membrane to the nucleus (2003) Cell, 113, pp. 685-700. , 10.1016/S0092-8674(03)00432-X, 12809600
  • de Caestecker, M., The transforming growth factor-β superfamily of receptors (2004) Cytokine Growth Factors Rev, 5, pp. 1-11
  • Sun, T., Xin, Z., Jin, Z., Wu, Y., Gong, Y., Effect of TGF-β/Smad signalling on Sertoli cell and possible mechanism related to complete Sertoli Cell-Only Syndrome (2008) Mol Cell Biochem, 319, pp. 1-7. , 10.1007/s11010-008-9869-3, 18648910
  • Zhao, G.Q., Hogan, B.L.M., Evidence that Mothers-against-dpp-related 1 (Madr1) plays a role in the initiation and maintenance of spermatogenesis in the mouse (1997) Mech Dev, 61, pp. 63-73. , 10.1016/S0925-4773(96)00622-3, 9076678
  • Pellegrini, M., Grimaldi, P., Rossi, P., Germia, R., Dolci, S., Development expression of BMP4/ALK3/Smad5 signaling pathway in the mouse testis: a potential role of BMP4 in spermatogonia differentiation (2003) J Cell Sci, 116, pp. 3363-3372. , 10.1242/jcs.00650, 12857787
  • Hu, J., Zhanf, Y.Q., Liu, X.P., Wang, R.A., Jin, Y., Xu, R.J., Expression and localization of Smad1, Smad2 and Smad4 proteins in rat testis during postnatal development (2003) Asian J Androl, 5, pp. 51-55
  • Gonzalez, C.R., Gonzalez, B., Rulli, S.B., Huhtaniemi, I., Calandra, R.S., Gonzalez-Calvar, S.I., TGF-beta1 System in Leydig Cells. Part I: Effect of hCG and Progesterone (2010) J Reprod Dev, 56, pp. 389-395. , 10.1262/jrd.09-166N, 20431248
  • Gonzalez, C.R., Gonzalez, B., Rulli, S.B., Dos Santos, M.L., Mattos Jardim Costa, G., França, L.R., Calandra, R.S., Gonzalez-Calvar, S.I., TGF-beta1 system in Leydig Cells. Part II: TGF-beta1 and Progesterone, Through Smad1/5, are Involved in the Hyperplasia/hypertrophy of Leydig Cells (2010) J Reprod Dev, 56, pp. 400-404. , 10.1262/jrd.09-167N, 20431251

Citas:

---------- APA ----------
Gonzalez, C.R., Matzkin, M.E., Frungieri, M.B., Terradas, C., Ponzio, R., Puigdomenech, E., Levalle, O.,..., Gonzalez-Calvar, S.I. (2010) . Expression of the TGF-beta1 system in human testicular pathologies. Reproductive Biology and Endocrinology, 8.
http://dx.doi.org/10.1186/1477-7827-8-148
---------- CHICAGO ----------
Gonzalez, C.R., Matzkin, M.E., Frungieri, M.B., Terradas, C., Ponzio, R., Puigdomenech, E., et al. "Expression of the TGF-beta1 system in human testicular pathologies" . Reproductive Biology and Endocrinology 8 (2010).
http://dx.doi.org/10.1186/1477-7827-8-148
---------- MLA ----------
Gonzalez, C.R., Matzkin, M.E., Frungieri, M.B., Terradas, C., Ponzio, R., Puigdomenech, E., et al. "Expression of the TGF-beta1 system in human testicular pathologies" . Reproductive Biology and Endocrinology, vol. 8, 2010.
http://dx.doi.org/10.1186/1477-7827-8-148
---------- VANCOUVER ----------
Gonzalez, C.R., Matzkin, M.E., Frungieri, M.B., Terradas, C., Ponzio, R., Puigdomenech, E., et al. Expression of the TGF-beta1 system in human testicular pathologies. Reprod. Biol. Endocrinol. 2010;8.
http://dx.doi.org/10.1186/1477-7827-8-148