The impact of busulfan on the testicular structure in prepubertal rats: A histological, ultrastructural and immunohistochemical study

El-Hay, Reem Ibrahim Abd; Hamed, Walaa H E; Omar, Nesreen Moustafa; El-Bassouny, Dalia R.; Gawish, Salwa A.

doi:10.1080/01913123.2023.2234470

Cited by 3 publications

(3 citation statements)

References 44 publications

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“…149 The notion that testicular dysfunction progressively recovers following busulfan-based treatment during childhood 70 is validated in murine preclinical models. 134,135 The three remaining agents (ifosfamide, chlorambucil, and melphalan) included in the CED equation and examined for prepubertal treatment lack studies on either the clinical or preclinical front. Among these, our assessment revealed ifosfamide as particularly concerning.…”

Section: Discussionmentioning

confidence: 99%

“…In prepubertal rats, a single dose of 40 mg/kg managed to impair germ, Sertoli, and Leydig cells up to 10 weeks after treatment, with a mild improvement 10 weeks later. 134 Likewise, in mice, a comparable injection of 45 mg/kg reduced germ cell count up to 8 weeks post-treatment, with density thereafter being comparable to untreated controls. The authors have also isolated spermatogonial cells 10 days after injecting mice with busulfan and noted that these could differentiate into post-meiotic stages when cultured in vitro in methylcellulose systems.…”

Section: Other Alkylating Agentsmentioning

confidence: 94%

“…70 No dose-dependent effect: No difference in the onset of infertility when stratified by a dose of <14 mg/kg and ≥16 mg/kg 71 ; No impact on pubertal development after cumulative doses of 16-20 mg/kg 162 Germ cells: Reduction in density, with recovery 10-20 weeks after treatment. 134,135 Treated spermatogonia can differentiate past meiotic stages. 135 Sertoli cells: Reduction in density and impairment of BTB integrity.…”

Section: Clinical Findings Preclinical Findingsmentioning

confidence: 99%

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Alkylating agents‐induced gonadotoxicity in prepubertal males: Insights on the clinical and preclinical front

Sriram,

Macedo,

Mavinkurve‐Groothuis

et al. 2024

Clinical Translational Sci

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Rising cure rates in pediatric cancer patients warrants an increased attention toward the long‐term consequences of the diagnosis and treatment in survivors. Chemotherapeutic agents can be gonadotoxic, rendering them at risk for infertility post‐survival. While semen cryopreservation is an option that can be provided for most (post)pubertal boys before treatment, this is unfortunately not an option prepubertal in age, simply due to the lack of spermatogenesis. Over the last couple of years, studies have thus focused on better understanding the testis niche in response to various chemotherapeutic agents that are commonly administered and their direct and indirect impact on the germ cell populations. These are generally compounds that have a high risk of infertility and have been classified into risk categories in curated fertility guidelines. However, with it comes the lack of evidence and the challenge of using informative models and conditions most reflective of the physiological scenario, in short, the appropriate study designs for clinically relevant outcomes. Besides, the exact mechanism(s) of action for many of these “risk” compounds as well as other agents is unclear. Understanding their behavior and effect on the testis niche will pave the way for incorporating new strategies to ultimately combat infertility. Of the various drug classes, alkylating agents pose the highest risk of gonadotoxicity as per previously established studies as well as risk stratification guidelines. Therefore, this review will summarize the findings in the field of male fertility concerning gonadotoxicity of akylating agents as a result of chemotherapy exposure.

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