Changes in the Vaginal Epithelium of the Rat after Vitamin A-Deficiency

Abstract
The changes occurring in the dry stained vaginal smears of castrate, non-castrate, and pregnant rats during the development of vitamin A-deficiency, and during repair of the deficiency state, are described. These observations are based upon the study of more than 52,000 vaginal smears. Lack of A results in an early cornification of the nucleated epithelial cells typical of the prooestrous smear, and in an accentuation of the process of cornification normally occurring at oestrus, resulting in the appearance of completely cornified smears during several successive days. The last day of such periods represents the stage of true oestrus, or ‘heat.’ There also occurs a progressive cornification and an increased proliferation of the nucleated epithelial cells of the dioestrous type of vaginal smears, associated with a corresponding reduction in the relative number of leucocytes, culminating in continuous and complete cornification of the smears before xerophthalmia and growth retardation become apparent. As a result, the cyclic changes of oestrus are represented by alternating periods of partial (metoestrus and dioestrus) and complete cornification (prooestrus and oestrus) of the vaginal smears. Until the two types of smear merge into a state of complete and continuous cornification, oestrous cycles of normal duration can be followed by the dry stained smears. Mucus disappears from the smear at the onset of cornification and reappears during the early stages of repair. Except in castrate rats, daily administration of one-tenth to one-fifth drop of cod liver oil usually effects repair of severe vaginal cornification during the second week of therapy, and represents the approximate minimal level of therapy for maintenance of normal vaginal smears in A-deficient rats. With larger doses of vitamin A, cornified cells disappear from the smear within 1 to 2 days. Small numbers of cornified cells continue to appear, in the vaginal smears of castrate rats, even after long periods of vitamin A-therapy, invalidating the use of such rats for assay tests by the smear method. The usefulness of the vaginal cornification test as a method of bio-assay, and as a criterion of mild levels of vitamin A-deficiency, is discussed.