The relationship between vitamin A deficiency and estrogen in producing uterine metaplasia in the rat

Abstract

SIX FIGURESMetaplasia of the lining and glandular epithelium of the uterus has been reported in intact vitamin A deficient rats (Wolbach and Howe, ' 2 5 ) . McCullough and Dalldorf ( '37) maintained that vitamin A deficiency was the primary requisite for uterine metaplasia and that estrone acted solely as a secondary factor. Bo ('55) did not observe metaplasia of uterine epithelium in ovariectomized vitamin A deficient rats and the results obtained indicated that before the manifestations of vitamin A deficiency can be expressed in the uterus, the ovaries by their endocrine function, must stimulate normal growth and function of that organ. It was, therefore, thought advisable to determine whether or not estrogen supplied to ovariectomized vitamin A deficient rats can effectively substitute for the ovary in the production of metaplasia of the uterine epithelium. This is a report of results of administration of estrogen to ovariectomized vitamin A deficient rats. MATERIALS AND METHODSNinety female rats of the Wistar strain were used in these experiments. The animals were 20 to 22 days of age and weighed approximately 35 to 40 gm when placed on the vita-

Variable Expression of Cellular Retinol- and Cellular Retinoic Acid-Binding Proteins in the Rat Uterus and Ovary during the Estrous Cycle1

“…Vitamin A deficiency in female rats also produces morphological changes in the luminal and glandular epithelium of the uterus. These changes do not occur with ovariectomy but do appear in vitamin A-deficient ovariectomized rats treated with estrogen [2], suggesting an interplay of vitamin A and ovarian hormones in normal reproductive function.…”

A Novel Short-Chain Alcohol Dehydrogenase from Rats with Retinol Dehydrogenase Activity, Cyclically Expressed in Uterine Epithelium1

“…However, constant stimulation by estrogen of vitamin A-deficient animals resulted in a dramatic induction of the vitamin A-deficient phenotype seen in normal, deficient animals [11]. During the normal estrous cycle, no proliferation of uterine epithelium is required unless the animal becomes pregnant, and in fact, the purpose of the cycle is simply to prepare the uterus for that event.…”

“…However, if the rats have been ovariectomized, making the uterus essentially quiescent, no keratinization is observed. If the ovariectomized animals are put under constant, exogenous estrogen stimulation to stimulate uterine growth, keratinization does occur, as in the normal, vitamin A-deprived rat that has continued to maintain the estrous cycle [11]. Interestingly, a recent report suggests that the mouse responds differently, with ovariectomy accelerating the metaplasia in the uterus of the vitamin A-deficient animal [12].…”

Implantation, Transplantation, and Epithelial-Mesenchymal Relationships in the Rat Uterus

“…The pseudostratified epithelium of the proliferative estrogenic phase and the secretory activity of the progestational phase of the estrus cycle are two familiar examples of its protean structure. In women the postmenstrual endometrium may undergo epidermoid or squamoid changes during its rapid regeneration (19), and in laboratory animals vitamin A deficiency and exogenous hormone administration may lead to what has been identified as extensive squamous metaplasia by some workers (20)(21)(22)(23)(24)(25)(26)(27). In the light of these various reports of the capacity of uterine epithelium to undergo squamous metaplasia, it was necessary to examine critically the possibility that what we had provisionally regarded as epidermis of migratory origin growing on the uterine mesenchymal substrate was, in fact, endometrial epithelium transformed under the influence of chronic estrogen administration.…”