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Mol. Hum. Reprod. Advance Access published online on October 7, 2009
Molecular Human Reproduction, doi:10.1093/molehr/gap087
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© The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Toxicants and human sperm chromatin integrity

Geraldine Delbès1, Barbara F. Hales1 and Bernard Robaire1,2

1Department of Pharmacology & Therapeutics, McGill University, Montréal, QC, Canada 2Department of Obstetrics & Gynecology McGill University, Montréal, QC, Canada

Correspondence to: Bernard Robaire Department of Pharmacology and Therapeutics, 3655 Promenade Sir-William-Osler, Montréal, Québec, Canada H3G 1Y6, Tel: (514) 398-3630, Fax: (514) 398-7120, E-mail: bernard.robaire{at}mcgill.ca

The integrity of the paternal genome is essential as the spermatozoon can bring genetic damage into the oocyte at fertilization and contribute to the development of abnormal pregnancy outcome. During the past two decades, many assays have been developed to measure sperm DNA strand breaks, chromatin structure and compaction, and assess the proteins associated with the DNA, as well as epigenetic modifications. Using these assays, it has been shown that exposure to physical agents or to chemicals, including therapeutic drugs and environmental toxicants, can affect the integrity of sperm chromatin, inducing structural, genetic and/or epigenetic abnormalities. The mechanisms by which such damage is triggered are still largely unresolved and the susceptibility of each individual will depend on their genetic background, lifestyle and exposure to various insults. Depending on the nature of the chemicals, they may directly target the DNA, induce an oxidative stress, or modify epigenetic elements. The significance of measuring sperm chromatin integrity comes from the fact that this endpoint correlates well with low IVF and ICSI outcomes, and idiopathic infertility. Nevertheless, it is hard to establish a direct link between paternal sperm chromatin integrity and the health of the future generations. Thus, it seems essential to undertake studies that will resolve the impact of chemical and environmental factors on chromatin structure and epigenetic components of human spermatozoa and to elucidate what sperm nuclear endpoints are predictors of the quality of progeny outcome.

Key Words: sperm DNA strand breaks/chromatin compaction/epigenetics/toxicants/male fertility

Submitted on August 13, 2009; resubmitted on September 27, 2009; accepted on October 2, 2009.


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