ArticleScientific reports2018
Chemotherapy drugs cyclophosphamide, cisplatin and doxorubicin induce germ cell loss in an in vitro model of the prepubertal testis.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Impacts of platinum-based chemotherapy on subsequent testicular function and fertility in boys with cancer.Human reproduction update · 2020Pooled it
- Doxorubicin and 4-Hydroperoxycyclophosphamide Alter Mitochondrial Dynamics and miR-34 Expression in Spermatogonia and Spermatocytes In Vitro.Basic & clinical pharmacology & toxicology · 2026Article
- SIRT7 links H3K36ac epigenetic regulation with genome maintenance in the mouse testis.Nature communications · 2026Article
- Exosomes in oncofertility: emerging roles in chemotherapy-induced reproductive damage and fertility preservation.Reproduction & fertility · 2026Review
- Testicular organoid models in male reproductive toxicology: advances, applications, and future perspectives.Frontiers in physiology · 2026Article
- Ferroptotic- and non-ferroptotic mechanisms associated with doxorubicin-induced male reproductive dysfunction.Toxicology reports · 2025Review
- In vivo and in vitro spermatogenesis in prepubertal mouse testes exposed to low gonadotoxic doses of cytarabine or Daunorubicin.Scientific reports · 2025Article
- Mesenchymal Stem Cell-Derived Small Extracellular Vesicle as A Novel Therapeutic Approach for Chemotherapy-Induced Male Infertility: A Review Article.International journal of fertility & sterility · 2025Article
- Organotypic culture system for prepubertal mice testicular tissue: A comparative study.Frontiers in endocrinology · 2025Article
- Germ cell quantification in human fetal and prepubertal testis tissues: a comparison of current methodologies.Reproduction & fertility · 2025Article
- The attenuation of doxorubicin-induced testicular toxicity with improved testicular histoarchitecture of mice by the bioactive compounds inToxicology reports · 2024Article
- Non-alkylating agents-induced gonadotoxicity in pre-pubertal males: Insights on the clinical and pre-clinical front.Clinical and translational science · 2024Review
- In vivo and in vitro sperm production: an overview of the challenges and advances in male fertility restoration.Clinical and experimental reproductive medicine · 2024Article
- Alkylating agents-induced gonadotoxicity in prepubertal males: Insights on the clinical and preclinical front.Clinical and translational science · 2024Review
- Eugenol Nanoparticles Ameliorate Doxorubicin-Induced Spermatogenic Dysfunction by Inhibiting the PINK1/Parkin and BNIP3/NIX Signaling Pathways.International journal of nanomedicine · 2024Article
- Mitigative potential of rhoifolin against cisplatin prompted testicular toxicity: biochemical, spermatogenic and histological based analysis.Toxicology research · 2023Article
- Culture-space control is effective in promoting haploid cell formation and spermiogenesis in vitro in neonatal mice.Scientific reports · 2023Article
- Granulocyte-colony stimulating factor does not prevent in vitro cisplatin-induced germ cell reduction in immature human and mouse testis.BMC cancer · 2023Article
- Protective/preventive effects of quercetin against cyclophosphamide-induced hepatic inflammation, apoptosis and fibrosis in rats.Hepatology forum · 2023Article
- Impact of endocrine disrupting chemicals and pharmaceuticals on Sertoli cell development and functions.Frontiers in endocrinology · 2023Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Long term survival rates for childhood cancers is steadily increasing, however cancer survivors can experience fertility problems as a consequence of chemotherapy treatment. This is particularly problematic for young boys, for whom no fertility preservation treatment is yet established. Here, we have determined the effects on prepubertal mouse testis of three commonly used chemotherapy drugs; cyclophosphamide (using its active metabolite phosphoramide mustard), cisplatin and doxorubicin, exposing testicular fragments to a clinically relevant range of concentrations in vitro. All three drugs induced a specific and highly significant loss of germ cells, including spermatogonial stem cells. In contrast, there was no significant effect on somatic cells, for either Sertoli or interstitial cells. Time course analysis of cleaved Caspase-3 expression showed a significant increase in apoptosis eight hours prior to a detectable decrease in germ cell numbers following exposure to phosphoramide mustard or cisplatin, although this pattern was not seen following doxorubicin-exposure. Moreover, analysis of DNA damage at 16 h showed increased γH2AX expression in response to all three drugs. Overall, results show that cisplatin, doxorubicin and cyclophosphamide all specifically induce loss of germ cells, including of spermatogonial stem cells, in the prepubertal mouse testis at concentrations relevant to human therapeutic exposures.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.