American Journal of Clinical Nutrition, Vol 5, 666-673, Copyright © 1957 by The American Society for Clinical Nutrition, Inc.

Relation of Vitamin A Deficiency and Estrogen to Induction of Keratinizing Metaplasia in the Uterus of the Rat

¹ From Department of Anatomy, School of Medicine, University of North Dakota, Grand Forks, North Dakota

Metaplasia of the uterine epithelium of estrogen-treated rats begins as many independent centers that grow and coalesce to produce a keratinized stratified squamous epithelium which replaces the original uterine epithelium.

The origin of epithelial metaplasia produced by estrogen stimulation differs from the metaplasia which occurs in vitamin A deficiency in that in the former the change takes origin in the luminal epithehium and the latter in the endometrial glands. The epithelium produced by estrogen stimulation is thicker and more heavily keratinized than that produced by vitamin A deficiency.

Keratinizing metaplasia in the uterus of the rat was observed to occur only in intact animals on a vitamin A-deficient diet or in the ovariectomized, vitamin A-deficient rats treated with estrogen. The results demonstrate that estrogen has an important role in producing keratinized epithelium in avitaminosis A and the change cannot be considered to be due to only a local vitamin A deficiency.

From the present investigation it can be concluded that vitamin A deficiency is not the primary factor in producing keratinizing metaplasia in the uterus of the rat since estrogen plays a role in producing the change.

The mode of action of vitamin A in maintaining normal uterine epithelium is not known, but it seems that a balance may exist between estrogen and vitamin A in order to maintain the integrity of the uterine epithelium and when this is disrupted keratinizing metaplasia occurs.

The abnormal cornification of the vagina that occurs in vitamin A deficiency of the rat was compared with the uterine changes and it was concluded that the two are not the same. In the vagina the change is more of a hyperplastic change while in the uterus it is a true metaplasia. Therefore, the conclusions drawn from the observations made on the vagina in avitaminosis A and between vitamin A and estrogen cannot be generalized to include the uterus.