Maternal restraint stress‐enhanced teratogenicity of all‐trans‐retinoic acid in CD‐1 mice

Abstract
The present study combined maternal restraint stress with a teratogenic agent, all-trans-retinoic acid (†RA). Five treatment groups were used initially: (1) vehicle (corn oil) control [C],(2) food/water-deprived [FWD], (3) †RA only [†RA](4)restraint only [R], and (5) †RA plus restraint [†RA+R] Mated CD-1 mice in groups 3 and 5 were given 20 mg/kg †RA po. Mice in groups 4 and 5 were restrained in the supine position for 12 hr (9:00 a.m. to 9.00 p.m.), and the FWD group mice were deprived during the same time period. The †RA+R mice were dosed immediately prior to the 12-hr restraint period. All treatments were administered on gestation day (GD) 9 (copulation plug = day 1). On GD 18, all females were killed and subjected to teratological examination. The incidences of resorptions, short tails, bent tails, fused ribs, and fused vertebrae were significantly increased in the †RA+R group, in comparison with all other groups. Spina bifida was observed only in the †RA+R group. The current results, combined with those of earlier studies with other agents, support the likelihood that maternal stress can exacerbate adverse effects of chemical teratogens on mouse development.