The cause of many of the adverse reproductive outcomes and developmental
diseases among offspring is not well understood. Most of the
epidemiologic and experimental animal research has focused on the
relationship between maternal exposures including medications, tobacco
smoke, alcohol, infections, and occupation and the occurrence of
spontaneous abortion, low birth weight, and birth defects. The potential
role of paternal exposures has not been investigated as extensively
despite long-standing animal research that demonstrates the induction of
mutations in the male germ cell after exposure to certain agents and
subsequent reproductive failure or early pregnancy loss. Given this
relative lack of interest, acquisition of epidemiologic data and the
development of a definitive model or mechanism for potential
male-mediated effects has been hindered. However, recent laboratory and
epidemiologic investigations have suggested that paternal exposures may
be more important than previously suspected. This topic has been termed
by some as "male-mediated developmental toxicity. " This is meant to
refer to the effects of exposures and other factors relating to the male
parent that result in toxicity to the conceptus and abnormal
development. The developmental endpoints of interest can include fetal
loss, congenital abnormalities, growth retardation, cancer, and
neurobehavioral effects. These effects may operate through a variety of
mechanisms including gene mutation, chromosomal aberrations, seminal
fluid transfer of toxicants and epigenetic events.
