Male-mediated developmental toxicity has been of concern for many years. The public became aware of male-mediated developmental
toxicity in the early 1990s when it was reported that men working at Sellafi eld might be causing leukemia in their children.
Human and animal studies have contributed to our current understanding of male-mediated effects. Animal studies in the 1980s
and 1990s suggested that genetic damage after radiation and chemical exposure might be transmitted to offspring. With the
increasing understanding that there is histone retention and modifi cation, protamine incorporation into the chromatin and DNA
methylation in mature sperm and that spermatozoal RNA transcripts can play important roles in the epigenetic state of sperm,
heritable studies began to be viewed differently. Recent reports using molecular approaches have demonstrated that DNA damage
can be transmitted to babies from smoking fathers, and expanded simple tandem repeats minisatellite mutations were found in
the germline of fathers who were exposed to radiation from the Chernobyl nuclear power plant disaster. In epidemiological studies,
it is possible to clarify whether damage is transmitted to the sons after exposure of the fathers. Paternally transmitted damage to
the offspring is now recognized as a complex issue with genetic as well as epigenetic components.

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