Effects of limited paternal exposure to xenobiotic agents on the development of progeny.

This report represents a series of investigations of the postnatal functional sequelae of paternal exposure to opioids and other xenobiotic agents. In separate studies, young adult male mice were exposed to (1) morphine; (2) levorphanol or its nonanalgesic isomer dextrorphan; or (3) 80% nitrous oxide/20% oxygen. Males (5-8/group) were injected twice daily for 5 1/2 or 8 1/2 days with opioids or saline, or received a single 4 hour inhalation exposure to nitrous oxide/oxygen or compressed air. At 6-8 1/2 days post-treatment, each male was housed with 3 drug-naive nulliparous females. With the exception of birth weights of litters, no alterations in reproductive indices were observed. Changes in reproductive endocrine parameters included marked attenuation of serum luteinizing hormone response to castration in both young adult (8 week) and older (18 week) F1 morphine offspring, when compared with saline-derived groups. The morphine progeny showed decrements in body weight and delayed onset of maturational indices through four generations of selective inbreeding. Similar developmental delays occurred in F1 offspring originating from paternal levorphanol, dextrorphan and nitrous oxide groups, when compared with their respective controls. Behavioral study of F1 offspring revealed alterations in: water maze performance and learning, if preceded by unavoidable footshock, in morphine offspring at 8 and 18 weeks; aberrant swim patterns in both levorphanol and dextrorphan progeny at 6 1/2 and 8 1/2 weeks. Nitrous oxide progeny showed a blunting of hypothermic response to pharmacologic challenge at 16 weeks, in comparison to compressed air controls.(ABSTRACT TRUNCATED AT 250 WORDS)