Gestational retinoic acid exposure in the rat: effects of sex, strain and exposure period

Abstract

Effects of gestational exposure to all- trans retinoic acid (RA) were assessed in the Long–Evans (hooded) and Sprague–Dawley (albino) rat strains. Two exposure periods were evaluated against vehicle controls. Both involved three consecutive daily per os doses of either 2.5 mg/kg RA on gestational days (GD) 11 through 13 or 10 mg/kg RA on GD 14 through 16. All assessments were conducted on at least one male and one female per litter. Substantial main effects of sex, strain and treatment were obtained, but with few significant interactions. Main effects of strain were found on surface righting, neonatal mortality, litter weight and postnatal day (PND) 35 regional brain weight. Among strain effects, the most interesting was the finding that weights of whole brain, frontal cortex, brainstem and cerebellar vermis were lower in hooded than in albino rats. These strain effects seldom interacted with treatment. Among the treatment effects was the finding that GD 11–13 but not GD 14–16 RA exposure impaired the righting reflex in both strains. Moreover, GD 11–13 exposure reduced weight of the cerebellar vermis more than did GD 14–16 RA exposure, while GD 14–16 RA exposure had greater impact on the weight of the cerebellar hemispheres than did GD 11–13 exposure. Covariate analysis suggested that these effects were independent of reductions in body weight. It is concluded that there are few strain or sex differences in the effects of gestational RA exposure, at least for the rat strains evaluated in this study.