Retinol in Addition to Retinoic Acid is Required for Successful Gestation in Vitamin A-Deficient Rats1

Vitamin A-deficient, pregnant rats resorb their fetuses around Day 15 of gestation even when given retinoic acid (RA) daily. This resorption is prevented by the administration of retinol. Retinol was found to be required no later than Day 10 of gestation, and up to 500 micrograms of retinol administered on Day 11 or later was not able to change the course of fetal resorption in these animals. Vitamin A-deficient pregnant rats supported on 40 micrograms all-trans-RA daily that are given 2 micrograms of retinol on Day 10 and then placed on a retinol-sufficient diet at 24 h after administration of the retinol dose gave birth to normal pups. When a single 2-micrograms dose of retinol was administered on Day 10 and the vitamin A-deficient, RA-supported animals continued on the deficient diet supplemented with RA, the fetal resorption did not occur and the fetuses appeared normal when examined on Day 20 of gestation. Experiments using radiolabeled retinol tracer indicated that while there was some accumulation of radioactivity through Day 14 in the fetus, the administered retinol was mostly eliminated from the animal by Day 16. Thus, retinol is clearly required by Day 10 for normal gestation.