Polychlorinated Biphenyls Affect Histone Modification Pattern in Early Development of Rats: A Role for Androgen Receptor-Dependent Modulation?

Abstract

Background: The epigenome represents an important target of environmental pollution. Early-life exposure to polychlorinated biphenyls (PCBs) modifies sex steroid enzymes and receptor transcription patterns. Steroid receptors, such as androgen receptor (AR), function as coregulators of histone modification enzymes. Aim: To clarify if a PCB early-life exposure might affect the epigenome in rat liver, we analyzed some histone post-translational modifications (H3K4me3 and H4K16Ac) and the corresponding histone remodeling enzymes, and the AR as a histone enzyme coregulator. Results: We observed a decrease of H4K16Ac and H3K4me3 levels, possibly linked to the induction of chromatin-modifying enzymes SirtT1 and Jarid1b, and a decrease of AR. PCBs also seem to induce AR transcriptional activity. Some of the observed effects are sex dimorphic. Conclusion: Our data suggest that an early-life exposure to PCB sometimes modifies the epigenome in the offspring liver in a dimorphic way. AR might be involved in modulating PCB effects on the epigenome.

KEYWORDS::

• androgen receptor
• endocrine disruptors
• epigenetics
• histone modifications
• Jarid1b
• polychlorinated biphenyls

Acknowledgements

The authors are grateful to O Mornati and M Lopez for their skillful technical assistance.

Financial & competing interests disclosure

Financial support from the University of Milan, through the project PUR, is gratefully acknowledged. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all experimental investigations.

Additional information

Funding

Financial support from the University of Milan, through the project PUR, is gratefully acknowledged. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.