Paternal exposures: impact on reproductive and developmental outcome. An overview.

Experimental and epidemiologic investigations document the adverse consequences of an array of paternal exposures on the development of subsequent offspring. Male-mediated abnormalities have been reported after exposure to therapeutic and recreational drugs, to chemicals in the workplace and environment and to ionizing radiation. The impact on progeny outcome includes: an increase in congenital malformations, spontaneous abortions, fetal resorptions; low birth weight; increase in childhood cancers; developmental, neurobehavioral, neuroendocrine, neurochemical abnormalities; effects in F2 generation progeny. Fertility is often unaffected. The comparative influence of genetic, epigenetic and nongenetic mechanisms in the etiology of paternally-mediated adverse outcomes is unknown. There is no a priori reason to assume that male-mediated effects are limited to the agents studied to date. The broad spectrum of alterations recorded after exposure to a variety of unrelated agents suggests the need for a more focused effort and multidisciplinary exploration of the potential impact of the male parent on reproductive outcome.