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

The present study combined maternal restraint stress with a teratogenic agent, all-trans-retinoic acid (tRA). Five treatment groups were used initially: (1) vehicle (corn oil) control [C], (2) food/water-deprived [FWD], (3) tRA only [tRA], (4) restraint only [R], and (5) tRA plus restraint [tRA+R]. Mated CD-1 mice in groups 3 and 5 were given 20 mg/kg tRA 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 tRA+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 tRA+R group, in comparison with all other groups. Spina bifida was observed only in the tRA+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.