Intergenerational sex-specific transcriptomic alterations in gonads of mice after parental lead exposure

Lead (Pb) exposure is known to influence gene expression across multiple tissues, potentially affecting germline biology and offspring development. This study investigated transcriptomic alterations in the gonads of F1 mice following four weeks of parental exposure to Pb‑contaminated soil. After exposure, breeding generated four experimental groups: ① exposed dams with unexposed sires, ② exposed sires with unexposed dams, ③both parents exposed, and ④ unexposed controls. Testes and ovaries were collected from 9‑week‑old offspring, and RNA sequencing was performed using Qiagen CLC Genomics Workbench to characterise transcriptional changes. Principal component analysis revealed distinct transcriptomic profiles in Groups 1-3 relative to controls, indicating that parental Pb exposure, whether maternal, paternal, or combined, shaped offspring gonadal gene expression. Heatmap clustering showed partial overlap between Male Group 3 and controls, although unique expression features remained evident. All exposed groups exhibited reduced overall transcript abundance when compared to controls. Males with maternal Pb exposure displayed the highest number of differentially expressed genes (DEGs), with gene ontology analysis highlighting alterations in immune‑related and enzymatic pathways. In contrast, males with both maternal and paternal exposure showed the fewest DEGs, though a greater proportion were located on the Y chromosome. These sex‑specific transcriptional patterns, particularly those observed in the offspring of exposed sires, suggest that Pb‑related molecular effects may arise independently of direct maternal transfer. While the underlying mechanisms remain uncertain, the findings raise the possibility that some effects could be transmitted through heritable pathways.