Decoding cytarabine-induced damage in the prepubertal testis: A multi-omics atlas of ecosystem and inheritance.
The study reports a multi-omics analysis of prepubertal mouse testes in which cytarabine exposure was associated with germ-cell depletion, somatic-cell and signaling changes, impaired reproductive measures, and molecular alterations in unexposed F1 offspring.
Open original publication →What the AI sees
The study reports a multi-omics analysis of prepubertal mouse testes in which cytarabine exposure was associated with germ-cell depletion, somatic-cell and signaling changes, impaired reproductive measures, and molecular alterations in unexposed F1 offspring.
Research significance
The reported mouse data support cytarabine-associated ferroptosis, replication arrest, redox imbalance, and testicular-niche stress as candidate contributors to gonadotoxicity; it remains an inference that targeting these pathways could preserve fertility without reducing antileukemic efficacy, and this requires intervention studies and human validation.
Source abstract
Pediatric leukemia therapies can compromise future fertility, particularly in prepubertal boys who cannot bank sperm. We used dose-response histology, endocrine and sperm analyses, bulk and single-cell RNA-seq, and metabolomics to map cytarabine (Ara-C) injury in prepubertal mouse testes. Ara-C caused seminiferous-tubule disruption, hormone suppression, sperm loss, spermatogonial depletion linked to ferroptosis and replication arrest, stress remodeling of Sertoli and Leydig cells, and altered intercellular signaling centered on Sertoli hubs. Unexposed F1 offspring retained inflammatory, nucleotide, and energy-metabolism changes, suggesting intergenerational imprinting after paternal exposure. These findings define cell-type-specific vulnerabilities in the developing testis and nominate redox balance, ferroptosis, Sertoli stress pathways, Leydig inflammatory signaling, and niche communication as targets for fertility-preserving strategies during pediatric chemotherapy.