Histone H4 acetylation is dysregulated in active seminiferous tubules adjacent to testicular tumours
Study question: Is histone H4 acetylation (H4ac) altered in the seminiferous tubules of patients affected by testicular tumours? Summary answer: A considerable dysregulation of H4ac was detected in the cells of the seminiferous tubules adjacent to testicular tumours of different aetiology and prior...
| Autores: | , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/218066 |
| Acceso en línea: | https://hdl.handle.net/2445/218066 |
| Access Level: | acceso abierto |
| Palabra clave: | Epigenètica Espermatogènesi Tumors Immunohistoquímica Epigenetics Spermatogenesis Immunohistochemistry |
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España |
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| dc.title.none.fl_str_mv |
Histone H4 acetylation is dysregulated in active seminiferous tubules adjacent to testicular tumours |
| title |
Histone H4 acetylation is dysregulated in active seminiferous tubules adjacent to testicular tumours |
| spellingShingle |
Histone H4 acetylation is dysregulated in active seminiferous tubules adjacent to testicular tumours Ballescà, Josep Lluís Epigenètica Espermatogènesi Tumors Immunohistoquímica Epigenetics Spermatogenesis Tumors Immunohistochemistry |
| title_short |
Histone H4 acetylation is dysregulated in active seminiferous tubules adjacent to testicular tumours |
| title_full |
Histone H4 acetylation is dysregulated in active seminiferous tubules adjacent to testicular tumours |
| title_fullStr |
Histone H4 acetylation is dysregulated in active seminiferous tubules adjacent to testicular tumours |
| title_full_unstemmed |
Histone H4 acetylation is dysregulated in active seminiferous tubules adjacent to testicular tumours |
| title_sort |
Histone H4 acetylation is dysregulated in active seminiferous tubules adjacent to testicular tumours |
| dc.creator.none.fl_str_mv |
Ballescà, Josep Lluís Barrachina Villalonga, Ferran Iglesia Rodriguez, Alberto de la Jodar Bifet, Meritxell Soler Ventura, Ada Mallofré i Gómez, Carme Rodríguez-Carunchio, Leonardo Goudarzi, Afsaneh Corral, Juan Manuel Castillo Corullón, Judit Oliva Virgili, Rafael |
| author |
Ballescà, Josep Lluís |
| author_facet |
Ballescà, Josep Lluís Barrachina Villalonga, Ferran Iglesia Rodriguez, Alberto de la Jodar Bifet, Meritxell Soler Ventura, Ada Mallofré i Gómez, Carme Rodríguez-Carunchio, Leonardo Goudarzi, Afsaneh Corral, Juan Manuel Castillo Corullón, Judit Oliva Virgili, Rafael |
| author_role |
author |
| author2 |
Barrachina Villalonga, Ferran Iglesia Rodriguez, Alberto de la Jodar Bifet, Meritxell Soler Ventura, Ada Mallofré i Gómez, Carme Rodríguez-Carunchio, Leonardo Goudarzi, Afsaneh Corral, Juan Manuel Castillo Corullón, Judit Oliva Virgili, Rafael |
| author2_role |
author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Epigenètica Espermatogènesi Tumors Immunohistoquímica Epigenetics Spermatogenesis Tumors Immunohistochemistry |
| topic |
Epigenètica Espermatogènesi Tumors Immunohistoquímica Epigenetics Spermatogenesis Tumors Immunohistochemistry |
| description |
Study question: Is histone H4 acetylation (H4ac) altered in the seminiferous tubules of patients affected by testicular tumours? Summary answer: A considerable dysregulation of H4ac was detected in the cells of the seminiferous tubules adjacent to testicular tumours of different aetiology and prior to any treatment, while no comparable alterations were observed in patients with disrupted spermatogenesis. What is known already: Altered H4ac levels have been associated with a variety of testicular pathological conditions. However, no information has been available regarding potential alterations in the spermatogenic cells adjacent to the neoplasia in testicular tumour patients. Study design, size, duration: A retrospective analysis using testicular sections from 33 men aged between 21 and 74 years old was performed. Three study groups were defined and subjected to double-blind evaluation: a control group with normal spermatogenesis (n = 6), patients with testicular tumours (n = 18) and patients with spermatogenic impairments (n = 8). One additional sample with normal spermatogenesis was used as a technical internal control in all evaluations. Participants/materials, setting, methods: Immunohistochemistry against H4ac and, when needed, Placental-like alkaline phosphatase and CD117, was performed on testicular sections. The H4ac H-score, based on the percentage of detection and signal intensity, was used as the scoring method for statistical analyses. Protein expression data from the Human Protein Atlas were used to compare the expression levels of predicted secreted proteins from testicular tumours with those present in the normal tissue. Main results and the role of chance: We revealed, for the first time, a dramatic disruption of the spermatogenic H4ac pattern in unaffected seminiferous tubule cells from different testicular tumour patients prior to any antineoplastic treatment, as compared to controls (P < 0.05). Since no similar alterations were associated with spermatogenic impairments and the in silico analysis revealed proteins potentially secreted by the tumour to the testicular stroma, we propose a potential paracrine effect of the neoplasia as a mechanistic hypothesis for this dysregulation. Limitations, reasons for caution: Statistical analyses were not performed on the hypospermatogenesis and Leydig cell tumour groups due to limited availability of samples. Wider implications of the findings: To the best of our knowledge, this is the first report showing an epigenetic alteration in cells from active seminiferous tubules adjacent to tumour cells in testicular tumour patients. Our results suggest that, despite presenting spermatogenic activity, the global epigenetic dysregulation found in the testicular tumour patients could lead to molecular alterations of the male germ cells. Since testicular tumours are normally diagnosed in men at reproductive age, H4ac alterations might have an impact when these testicular tumour patients express a desire for fatherhood. Study funding/competing interest(s): This work was supported by the European Union Marie Curie European Training Network actions and by grants to R.O. from the 'Ministerio de Economía y Competividad (Spain)' (fondos FEDER 'una manera de hacer Europa', PI13/00699, PI16/00346 and PI20/00936) and from EU-FP7-PEOPLE-2011-ITN289880. J.C. was supported by the Sara Borrell Postdoctoral Fellowship, Acción Estratégica en Salud, CD17/00109. J.C. is a Serra Húnter fellow (Universitat de Barcelona, Generalitat de Catalunya). F.B. has received grants from the Ministerio de Educación, Cultura y Deporte para la Formación de Profesorado Universitario (Spain) (FPU15/02306). A.d.l.I. is supported by a fellowship of the Ministerio de Economía, Industria y Competitividad (Spain) (PFIS, FI17/00224). M.J. is supported by the Government of Catalonia (Generalitat de Catalunya, pla estratègic de recerca i innovació en salut, PERIS 2016-2020, SLT002/16/00337). The authors have no conflicts of interest to declare. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion |
| format |
article |
| status_str |
acceptedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/218066 |
| url |
https://hdl.handle.net/2445/218066 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Versió postprint del document publicat a: https://doi.org/10.1093/humrep/deac130 Human Reproduction, 2022, vol. 37, num.8, p. 1712-1726 https://doi.org/10.1093/humrep/deac130 |
| dc.rights.none.fl_str_mv |
(c) Barrachina F et al., 2022 info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
(c) Barrachina F et al., 2022 |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
European Society of Human Reproduction and Embryology |
| publisher.none.fl_str_mv |
European Society of Human Reproduction and Embryology |
| dc.source.none.fl_str_mv |
Articles publicats en revistes (Biomedicina) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
| instname_str |
Universidad de Barcelona |
| reponame_str |
Dipòsit Digital de la UB |
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Dipòsit Digital de la UB |
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|
| repository.mail.fl_str_mv |
|
| _version_ |
1869417812785627137 |
| spelling |
Histone H4 acetylation is dysregulated in active seminiferous tubules adjacent to testicular tumoursBallescà, Josep LluísBarrachina Villalonga, FerranIglesia Rodriguez, Alberto de laJodar Bifet, MeritxellSoler Ventura, AdaMallofré i Gómez, CarmeRodríguez-Carunchio, LeonardoGoudarzi, AfsanehCorral, Juan ManuelCastillo Corullón, JuditOliva Virgili, RafaelEpigenèticaEspermatogènesiTumorsImmunohistoquímicaEpigeneticsSpermatogenesisTumorsImmunohistochemistryStudy question: Is histone H4 acetylation (H4ac) altered in the seminiferous tubules of patients affected by testicular tumours? Summary answer: A considerable dysregulation of H4ac was detected in the cells of the seminiferous tubules adjacent to testicular tumours of different aetiology and prior to any treatment, while no comparable alterations were observed in patients with disrupted spermatogenesis. What is known already: Altered H4ac levels have been associated with a variety of testicular pathological conditions. However, no information has been available regarding potential alterations in the spermatogenic cells adjacent to the neoplasia in testicular tumour patients. Study design, size, duration: A retrospective analysis using testicular sections from 33 men aged between 21 and 74 years old was performed. Three study groups were defined and subjected to double-blind evaluation: a control group with normal spermatogenesis (n = 6), patients with testicular tumours (n = 18) and patients with spermatogenic impairments (n = 8). One additional sample with normal spermatogenesis was used as a technical internal control in all evaluations. Participants/materials, setting, methods: Immunohistochemistry against H4ac and, when needed, Placental-like alkaline phosphatase and CD117, was performed on testicular sections. The H4ac H-score, based on the percentage of detection and signal intensity, was used as the scoring method for statistical analyses. Protein expression data from the Human Protein Atlas were used to compare the expression levels of predicted secreted proteins from testicular tumours with those present in the normal tissue. Main results and the role of chance: We revealed, for the first time, a dramatic disruption of the spermatogenic H4ac pattern in unaffected seminiferous tubule cells from different testicular tumour patients prior to any antineoplastic treatment, as compared to controls (P < 0.05). Since no similar alterations were associated with spermatogenic impairments and the in silico analysis revealed proteins potentially secreted by the tumour to the testicular stroma, we propose a potential paracrine effect of the neoplasia as a mechanistic hypothesis for this dysregulation. Limitations, reasons for caution: Statistical analyses were not performed on the hypospermatogenesis and Leydig cell tumour groups due to limited availability of samples. Wider implications of the findings: To the best of our knowledge, this is the first report showing an epigenetic alteration in cells from active seminiferous tubules adjacent to tumour cells in testicular tumour patients. Our results suggest that, despite presenting spermatogenic activity, the global epigenetic dysregulation found in the testicular tumour patients could lead to molecular alterations of the male germ cells. Since testicular tumours are normally diagnosed in men at reproductive age, H4ac alterations might have an impact when these testicular tumour patients express a desire for fatherhood. Study funding/competing interest(s): This work was supported by the European Union Marie Curie European Training Network actions and by grants to R.O. from the 'Ministerio de Economía y Competividad (Spain)' (fondos FEDER 'una manera de hacer Europa', PI13/00699, PI16/00346 and PI20/00936) and from EU-FP7-PEOPLE-2011-ITN289880. J.C. was supported by the Sara Borrell Postdoctoral Fellowship, Acción Estratégica en Salud, CD17/00109. J.C. is a Serra Húnter fellow (Universitat de Barcelona, Generalitat de Catalunya). F.B. has received grants from the Ministerio de Educación, Cultura y Deporte para la Formación de Profesorado Universitario (Spain) (FPU15/02306). A.d.l.I. is supported by a fellowship of the Ministerio de Economía, Industria y Competitividad (Spain) (PFIS, FI17/00224). M.J. is supported by the Government of Catalonia (Generalitat de Catalunya, pla estratègic de recerca i innovació en salut, PERIS 2016-2020, SLT002/16/00337). The authors have no conflicts of interest to declare.European Society of Human Reproduction and Embryology2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/218066Articles publicats en revistes (Biomedicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1093/humrep/deac130Human Reproduction, 2022, vol. 37, num.8, p. 1712-1726https://doi.org/10.1093/humrep/deac130(c) Barrachina F et al., 2022info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2180662026-05-27T06:46:51Z |
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15,812455 |