Adverse effects of paternal opiate exposure on offspring development and sensitivity to morphine-induced analgesia

We have shown previously that chronic morphine administration to adolescent male rats produced a number of gender specific deficits in their offspring. The purpose of the present studies was to extend our earlier observations by examining the acute, direct effects of morphine exposure to male rats on their fertility and the development of viable offspring. Sexually mature male rats were injected with a single dose of morphine (25 mg/kg) and 24 hr later were bred with drug-naive females. Fertility rates (vaginal plugs and pregnancies) were monitored throughout the breeding period as was the development of the offspring. Our results showed that a large, acute dose of morphine given to drug-naive male rats 24 hr before the initiation of breeding had no effect on fertility rates, but produced several adverse effects on fetal outcome. Litter sizes in morphine-derived offspring were considerably smaller than in controls and mortality rates were more than 6 times higher. Moreover, morphine-derived male, but not female, offspring had a significantly enhanced sensitivity to the antinociceptive effects of morphine. Collectively, these data suggest that acute paternal morphine exposure just before breeding with drug-naive females had no effect on fertility, but exerted negative effects on the viability and development of their offspring. These results represent the most compelling evidence to date that paternal opiate exposure can adversely affect fetal outcome and are particularly striking in that they were produced by a single injection of morphine. We are aware of no animal studies, clinical cases or anecdotal reports in humans in which such a phenomenon has been described.