Histologic Analysis of Testes from Prepubertal Patients Treated with Chemotherapy Associates Impaired Germ Cell Counts with Cumulative Doses of Cyclophosphamide, Ifosfamide, Cytarabine, and Asparaginase.

Data de publicació: 01/02/2021 Data Ahead of Print: 04/11/2020

Autors de IIS La Fe

Jose Vicente Medrano Plaza

Autor
David Hervás Marín

Autor
Teresa Vilanova Perez

Autor
Ana Navarro Gómez-Lechón

Autor
Antonio Pellicer Martínez

Autor
María Del Mar Andrés Moreno

Autor
Edurne Novella Maestre

Autor

Autors aliens a IIS La Fe

Goossens, E.

Grups d'Investigació

Biología Reproductiva y Bioingeniería en Reproducción Humana

Leader

Nicolás Garrido Puchalt
Investigación Clínica y Traslacional en Cáncer

Leader

José Gómez Codina
Medicina Reproductiva

Investigador Principal

José Morales Roselló

Abstract

Cryopreservation of immature testicular tissue is an experimental strategy for the preservation of fertility in prepubertal boys that will be subjected to a gonadotoxic onset, as is the case of oncologic patients. Therefore, the objective of this study was to assess the impact of chemotherapeutic treatments on the testicular histologic phenotype in prepubertal patients. A total of 56 testicular tissue samples from pediatric patients between 0 and 16 years old (28 with at least one previous chemotherapeutic onset and 28 untreated controls) were histologically analyzed and age-matched compared. At least two 5-µm sections from testis per patient separated by a distance of 100 µm were immunostained for the germ cell marker VASA, the spermatogonial markers UTF1, PLZF, UCHL1, and SALL4, the marker for proliferative cells KI67, and the Sertoli cell marker SOX9. The percentage of tubule cross-sections positive for each marker and the number of positive cells per tubule cross-section were determined and association with the cumulative dose received of each chemotherapeutic drug was statistically assessed. Results indicated that alkylating agents, cyclophosphamide and ifosfamide, but also the antimetabolite cytarabine and asparaginase were associated with a decreased percentage of positive tubules and a lower number of positive cells per tubule for the analyzed markers. Our results provide new evidences of the potential of chemotherapeutic agents previously considered to have low gonadotoxic effects such as cytarabine and asparaginase to trigger a severe testicular phenotype, hampering the potential success of future fertility restoration in experimental programs of fertility preservation in prepubertal boys.

Dades de la publicació

ISSN/ISSNe:: 1933-7191, 1933-7205
Tipus:: Article
Pàgines:: 603-613
DOI:: 10.1007/s43032-020-00357-6
PubMed:: 33150486
Factor d'Impacte:: 0,642 SCImago ℠
Quartil:: Q2 SCImago ℠

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Filiacions

Medrano, V, Jose:: Instituto de Investigación. Instituto de Investigación Sanitaria La Fe (IIS La Fe), Av. Fernando Abril Martorell, 106. Tower A, Lab. 6.22, 46026, Valencia, Spain.
Hervas, D.:: Instituto de Investigación. Instituto de Investigación Sanitaria La Fe (IIS La Fe), Av. Fernando Abril Martorell, 106. Tower A, Lab. 6.22, 46026, Valencia, Spain

Instituto de Investigación. Medrano, Jose, V , Inst Invest Sanitaria La Fe IIS La Fe, Av Fernando Abril Martorell,106 Tower,Lab 6-22, Valencia 46026, Spain
Vilanova-Perez, T.:: Instituto de Investigación. Instituto de Investigación Sanitaria La Fe (IIS La Fe), Av. Fernando Abril Martorell, 106. Tower A, Lab. 6.22, 46026, Valencia, Spain

Instituto de Investigación. Medrano, Jose, V , Inst Invest Sanitaria La Fe IIS La Fe, Av Fernando Abril Martorell,106 Tower,Lab 6-22, Valencia 46026, Spain
Navarro-Gomezlechon, A.:: Instituto de Investigación. Instituto de Investigación Sanitaria La Fe (IIS La Fe), Av. Fernando Abril Martorell, 106. Tower A, Lab. 6.22, 46026, Valencia, Spain

Instituto de Investigación. Medrano, Jose, V , Inst Invest Sanitaria La Fe IIS La Fe, Av Fernando Abril Martorell,106 Tower,Lab 6-22, Valencia 46026, Spain
Goossens, E.:: Vrije Universiteit Brussel (VUB), 1090, Brussels, Belgium

Vrije Univ Brussel VUB, B-1090 Brussels, Belgium
Pellicer, A.:: Instituto de Investigación. Instituto de Investigación Sanitaria La Fe (IIS La Fe), Av. Fernando Abril Martorell, 106. Tower A, Lab. 6.22, 46026, Valencia, Spain

Fundación IVI, 46026, Valencia, Spain

Instituto de Investigación. Medrano, Jose, V , Inst Invest Sanitaria La Fe IIS La Fe, Av Fernando Abril Martorell,106 Tower,Lab 6-22, Valencia 46026, Spain

Fdn IVI, Valencia 46026, Spain
Andres, M. M.:: Instituto de Investigación. Instituto de Investigación Sanitaria La Fe (IIS La Fe), Av. Fernando Abril Martorell, 106. Tower A, Lab. 6.22, 46026, Valencia, Spain

Hospital Universitario y Politécnico La Fe, 46026, Valencia, Spain

Instituto de Investigación. Medrano, Jose, V , Inst Invest Sanitaria La Fe IIS La Fe, Av Fernando Abril Martorell,106 Tower,Lab 6-22, Valencia 46026, Spain

Hosp Univ & Politecn La Fe, Valencia 46026, Spain
Novella-Maestre, E.:: Instituto de Investigación. Instituto de Investigación Sanitaria La Fe (IIS La Fe), Av. Fernando Abril Martorell, 106. Tower A, Lab. 6.22, 46026, Valencia, Spain

Hospital Universitario y Politécnico La Fe, 46026, Valencia, Spain

Instituto de Investigación. Medrano, Jose, V , Inst Invest Sanitaria La Fe IIS La Fe, Av Fernando Abril Martorell,106 Tower,Lab 6-22, Valencia 46026, Spain

Hosp Univ & Politecn La Fe, Valencia 46026, Spain