All-trans retinoic acid and 13-cis-retinoic acid in the rat whole-embryo culture: abnormal development due to the all-trans isomer.

9.5-day-old rat embryos were exposed to 3 micrograms 13-cis retinoic acid (13-cis-RA)/ml culture medium or 1 microgram all-trans retinoic acid (all-trans-RA)/ml culture medium for different time intervals of the culture period (test substance-exposure periods alternated with test substance-free periods). These studies were performed to confirm the hypothesis (Klug et al. 1989) that the effect of 13-cis-RA on embryonic development in vitro is predominantly caused by its isomerisation to all-trans-RA. A 12 h exposure of the rat embryos to 13-cis-RA during different periods of culture did not interfere with normal development. However, a 12 h exposure of the embryos to all-trans-RA in the first three quarters of the culture period significantly interfered with normal development and caused clear-cut and typical abnormalities. Embryonic exposure to 13-cis-RA, for periods of more than 12 h, caused severe interference with normal development and led to branchial effects very similar to those observed following to a 12 h exposure to all-trans-RA.