Evidence for a role of paternal exposures in developmental toxicity.: PATERNALLY MEDIATED DEVELOPMENTAL TOXICITY

International audienceExperimental evidence from radiation exposure, antimitotic drugs or chemicals such as pesticides or metals does suggest the possibility of transmission of paternally mediated developmental effects across generations. The mechanistic framework is growing with suggestion of transmission of epigenetic modifications as a mechanism alternative to germ-line mutagenesis. There is also ample experimental evidence for a specific susceptibility of the male embryo to the action of endocrine disrupters. In parallel, interpretation of epidemiological findings regarding effects of well-characterized paternal exposures, such as ionizing radiation or persistent organic pollutants (dioxins), on intrauterine development remains equivocal. Many epidemiological studies have included paternal exposures as an add-on to existing studies and focused mainly on birth defects, sex ratio, childhood cancers or spontaneous abortions. Functional alterations such as neurobehavioural parameters or reproductive dysfunction resulting from paternal exposure have been barely studied. Improved knowledge on possible consequences of paternal exposures in future generations is needed and has strong implication in terms of regulation, in the workplace for instance. One may expect human studies to be conducted with a particular focus on male-mediated developmental toxicity making use of biological markers pertinent to hypothesized mechanisms. Recognition of early determinants of disease onset has led to the setup of a number of mother-child cohorts across the world and careful assessment of paternal exposures should be included in these studies. These cohorts will also have the power to evaluate the specific impact of in utero exposure on a number of endpoints of developmental toxicity in males