Stability of the glandular morphogenesis produced by retinoids in the newborn hamster cheek pouch in vitro.

Retinoids can induce alterations in differentiation and morphogenesis in the hamster cheek pouch. In order to determine the stability of these changes, explants of neonatal pouch were exposed to 6 micrograms/ml of either retinyl acetate (RAc: 1.8 x 10(-5) M) or all-trans retinoic acid (RA: 2.0 x 10(-5) M) for an initial 3 of 7 days, out of a total of 21 days in organ culture. Three days of RAc or RA caused a delay in the differentiation and keratinization of the epithelium at least up to day 7 of culture. Additionally, two out of ten explants exposed to RA showed small downgrowths of epithelium into the stroma at 7 or 14 days. Seven days of exposure to either retinoid led to inhibition of epithelial keratinization, and produced a mucous metaplasia which was still seen at the end of the 21-day culture period. Periodic acid-Schiff (PAS)-positive, diastase-resistant material was present in the metaplastic epithelium, in intercellular, and in some instances, intracellular locations. An excess of either RAc or RA, for 7 days, induced persistent glandlike downgrowths of epithelium, suggesting that a stable alteration in the developmental program of the epithelium may have occurred. Many of these downgrowths possessed a lumen which was lined by cuboidal epithelium and contained PAS-positive, diastase-resistant secretory material. RA appeared more potent than RAc in inhibiting keratinization, in producing a mucous metaplasia, and in initiating glandlike downgrowths. The persistence of glandular downgrowths suggests that retinoids, either directly or indirectly, act in a manner similar to that of an embryonic inductor.