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

Reproductive sciences (Thousand Oaks, Calif.), 2021-02, Vol.28 (2), p.603-613 [Peer Reviewed Journal]

Society for Reproductive Investigation 2020 ;ISSN: 1933-7191 ;EISSN: 1933-7205 ;DOI: 10.1007/s43032-020-00357-6 ;PMID: 33150486

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Title:
Histologic Analysis of Testes from Prepubertal Patients Treated with Chemotherapy Associates Impaired Germ Cell Counts with Cumulative Doses of Cyclophosphamide, Ifosfamide, Cytarabine, and Asparaginase
Author: Medrano, Jose V. ; Hervás, D. ; Vilanova-Pérez, T. ; Navarro-Gomezlechon, A. ; Goossens, E. ; Pellicer, A. ; Andrés, M. M. ; Novella-Maestre, E.
Subjects: Adolescent ; Age Factors ; Antineoplastic Agents - adverse effects ; Asparaginase - adverse effects ; Belgium ; Case-Control Studies ; Child ; Child, Preschool ; Cyclophosphamide - adverse effects ; Cytarabine - adverse effects ; DEAD-box RNA Helicases - metabolism ; Embryology ; Fertility - drug effects ; Fertility Preservation ; Humans ; Ifosfamide - adverse effects ; Infertility, Male - chemically induced ; Infertility, Male - metabolism ; Infertility, Male - pathology ; Infertility, Male - physiopathology ; Ki-67 Antigen - metabolism ; Male ; Male Reproduction: Original Article ; Medicine ; Medicine & Public Health ; Nuclear Proteins - metabolism ; Obstetrics/Perinatology/Midwifery ; Pilot Projects ; Promyelocytic Leukemia Zinc Finger Protein - metabolism ; Reproductive Medicine ; Risk Assessment ; SOX9 Transcription Factor - metabolism ; Spain ; Spermatozoa - drug effects ; Spermatozoa - metabolism ; Spermatozoa - pathology ; Testis - drug effects ; Testis - metabolism ; Testis - pathology ; Testis - physiopathology ; Trans-Activators - metabolism ; Transcription Factors - metabolism ; Ubiquitin Thiolesterase - metabolism
Is Part Of: Reproductive sciences (Thousand Oaks, Calif.), 2021-02, Vol.28 (2), p.603-613
Description: 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.
Publisher: Cham: Springer International Publishing
Language: English
Identifier: ISSN: 1933-7191
EISSN: 1933-7205
DOI: 10.1007/s43032-020-00357-6
PMID: 33150486
Source: MEDLINE
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Histologic Analysis of Testes from Prepubertal Patients Treated with Chemotherapy Associates Impaired Germ Cell Counts with Cumulative Doses of Cyclophosphamide, Ifosfamide, Cytarabine, and Asparaginase

Society for Reproductive Investigation 2020 ;ISSN: 1933-7191 ;EISSN: 1933-7205 ;DOI: 10.1007/s43032-020-00357-6 ;PMID: 33150486

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