Reproductive toxicity of BioThrax in rabbits.

BACKGROUND: An increasing number of women are being vaccinated during child-bearing years, including vaccination with BioThrax (Anthrax Vaccine Adsorbed, or AVA). As only a limited number of studies exist in humans that have examined the effects of AVA on reproductive health, this study was conducted in order to evaluate the impact AVA vaccination may have on pregnant female rabbits and their offspring. METHODS: Two hundred female rabbits were vaccinated with saline, adjuvant, or AVA twice prior to mating and on one of two occasions during gestation, in order to have exposure to the antigen during organogenesis. Blood samples were collected from does and fetuses/kits to assess the development and in utero transfer of antibodies to Bacillus anthracis protective antigen (anti-PA IgG). Half of the does underwent Caesarean-sectioning on gestation day 29 and a gross necropsy was performed on both the does and their fetuses. The other half were allowed to naturally deliver and gross necropsy of the does and their kits was performed on lactation day 29. RESULTS: ELISA results showed that anti-PA IgG was generated by the does and passed to the fetuses/kits at detectable levels. CONCLUSIONS: AVA directly, or indirectly through the production of anti-PA IgG, did not appear to have an adverse effect on the pregnant females or their offspring, as measured by mating and fertility indices, natural delivery observations, clinical signs, gross lesions, in utero growth and survival, morphological development, or kit viability.

Effects of thalidomide on reproductive function and early embryonic development in male and female New Zealand white rabbits.

BACKGROUND: The present work was performed to determine the effect of thalidomide exposure on reproductive function and early embryonic development. METHODS: Twenty-five female New Zealand White rabbits were orally gavaged with 0, 10, 50, or 100 mg/kg/day thalidomide 14 days prior to mating through to gestation day 7 for a total of 22 days. Treated females were Caesarean-sectioned approximately 29 days after the date of attempted mating. Following mating with treated females, male rabbits (25/dose) were gavaged with 0, 30, 150, or 500 mg/kg/day beginning 14 days prior to mating with a group of untreated females (25/dose). Doses were administered through mating until the day before sacrifice for a minimum of 56 days. Untreated females were Caesarean-sectioned 29 days after the last attempted mating. Comprehensive necropsy and histopathology of the reproductive system were performed. RESULTS: Treated females had reduction in body weight gain during gestation. Mating and pregnancy parameters were unaffected by thalidomide. At 100 m/kg, litter averages for corpora lutea, implantations, litter sizes, does with viable fetuses and live fetuses decreased and the number of early resorptions, does with any resorptions, does with all conceptuses resorbed, and the percent resorbed conceptuses per litter increased. The number of early resorptions, the average number of early resorptions per litter, and the percent resorbed conceptuses per litter increased at 10 and 50 mg/kg. There were no thalidomide-related external fetal malformations. Mating and fertility in male rabbits were unaffected by thalidomide. There was an increased incidence of flaccid testes at 150 and 500 mg/kg and of bilateral small testes in all treated groups. At 500 mg/kg, there was degeneration of the germinal epithelium of the testicles with an increase in multinucleated giant cells in seminiferous tubule and a loss of round and elongating spermatids. CONCLUSIONS: Thalidomide had no adverse effects on mating and fertility in male and female rabbits dosed up to 500 and 100 mg/kg/day, respectively, for 14 days prior to mating. After 56 day of dosing, histopathologic changes with no associated sperm abnormalities were observed in the testicles. Embryonic development NOAEL for treated females mated to untreated males was <10 mg/kg. Corresponding fertility NOAEL for treated males mated to untreated females was 500 mg/kg.