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Published on: September 28, 2017
Paternal irradiation perturbs the expression of circadian genes in offspring
Andre M G F Gomes1, Ruth C Barber1, Yuri E Dubrova1
1Department of Genetics, University of Leicester, Leicester LE1 7RH, United Kingdom.
Abstract:
The circadian system represents a complex network which influences the timing of many biological processes. Recent studies have established that circadian alterations play an important role in the susceptibility to many human diseases, including cancer. Here we report that paternal irradiation in mice significantly affects the expression of genes involved in rhythmic processes in their first-generation offspring. Using microarrays, the patterns of gene expression were established for brain, kidney, liver and spleen samples from the non-exposed offspring of irradiated CBA/Ca and BALB/c male mice. The most over-represented categories among the genes differentially expressed in the offspring of control and irradiated males were those involved in rhythmic process, circadian rhythm and DNA-dependent regulation of transcription. The results of our study therefore provide a plausible explanation for the transgenerational effects of paternal irradiation, including increased transgenerational carcinogenesis described in other studies.
Insights
Paternal irradiation alters gene expression in offspring, affecting circadian rhythms and DNA transcription. This provides insight into transgenerational effects like increased cancer susceptibility.
Area of Science:
- Genetics
- Chronobiology
- Epigenetics
Background:
- Circadian system regulates biological timing and is implicated in disease susceptibility.
- Altered circadian rhythms are linked to various human diseases, including cancer.
- Paternal environmental exposures can impact offspring health across generations.
Purpose of the Study:
- To investigate the effects of paternal irradiation on gene expression in the first-generation offspring.
- To identify specific biological pathways affected by paternal irradiation in offspring.
- To explore the link between paternal irradiation, circadian rhythm gene expression, and transgenerational effects.
Main Methods:
- Gene expression profiling using microarrays in brain, kidney, liver, and spleen tissues.
- Analysis of non-exposed offspring from irradiated and control male mice (CBA/Ca and BALB/c strains).
- Statistical analysis to identify over-represented gene categories and pathways.
Main Results:
- Paternal irradiation significantly altered gene expression patterns in offspring.
- Genes involved in rhythmic processes, circadian rhythm, and DNA-dependent transcription were differentially expressed.
- Specific over-represented categories were identified in offspring of irradiated males compared to controls.
Conclusions:
- Paternal irradiation induces changes in the expression of circadian rhythm-related genes in offspring.
- These molecular alterations offer a potential explanation for transgenerational effects of paternal irradiation.
- Findings suggest a mechanism linking paternal irradiation to increased transgenerational carcinogenesis.
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