Omics · study · 2026
Doxorubicin induces immediate transcriptional change and apoptosis in spermatogonia from prepubertal rats.
Listed in NCBI GEO
Chemotherapy can compromise the fertility of boys with cancer, yet no standard protocols exist to preserve their reproductive potential.
Description
Before puberty, germ cells are almost exclusively spermatogonia that can be the target of anticancer drugs. Doxorubicin (DXO), a widely used anthracycline in pediatric oncology, has been associated with infertility in adulthood, but its immediate effects on prepubertal germ cells remain poorly understood.
In the present study, a preclinical rat model of prepubertal DXO exposure was developed to characterize the mechanisms underlying immediate DXO-induced germ cell damage. Six-day-old pups, received a single intraperitoneal injection of DXO (5 mg/kg) and effects were measure after 24 or 48 h. DXO exposure significantly reduced relative testis weight from 24 h and significantly increased apoptosis and germ cell loss at 48 h, while circulating testosterone remained unchanged, suggesting a selective germline effect.
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RNA-seq was done on GFP-positive germ cells purified at 24 h. Transcriptomic analysis confirmed the enrichment in spermatogonial stem cells (SSCs) in the GFP-sorted population. Moreover, DXO induced 51 differentially expressed genes (49 upregulated, 2 down regulated) that were mostly related the p53-dependant apoptosis pathway.
Pro-apoptotic genes (Cdkn1a, Bbc3/Puma, Tp53inp1, Fas) and oxidative stress regulators (Sesn2, Eda2r, Abhd4) were induced, whereas DNA repair genes (Mgmt, Xrcc1, Polh, Gadd45α, ...) were not activated. Our data revealed the DXO-induced immediate transcriptomic response after 24h, leading to germ cell death observed by histology at 48h. These findings suggest that SSCs respond to DXO by favoring apoptosis and stress regulation, a strategy that may preserve germline integrity and reduce the risk of transmitting genetic damage to the next generation.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE312nnn/GSE312922 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE312922 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1377600 ncbi.nlm.nih.gov/bioproject/PRJNA1377600 ↗
project · from NCBI GEO
- PubMed 41762288 pubmed.ncbi.nlm.nih.gov/41762288 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Rattus norvegicus
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75% · RNA sequencing 65%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE312922 | 15 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[organism].NCBITaxon:10116 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |