Glandular metaplasia of hair follicles and other responses to vitamin A excess in cultures of rodent skin

Abstract

This paper reports the effects of excess vitamin A on the development of hair follicles in organotypic cultures of embryonic mouse skin. Pieces of trunk skin, upper lip and lower jaw were cultivated on the surface of a clot of adult cock plasma and chicken embryo extract in slide preparations for 11 – 14 days. Changes in individual living follicles were observed daily and the findings confirmed from complete serial sections. In skin from the trunk of -day embryos the pelage follicles were initiated and underwent some normal differentiation, both in the presence and absence of added vitamin A (6·2 – 37·5 i.u./ml.). In skin from the trunk of 15-day embryos the pelage follicles differentiated normally for 4 days in both treated and untreated groups but then regressed in the vitamin-treated groups (12·5, 25·0 i.u./ml.), while normal differentiation continued and some keratinized hairs were formed in the control groups. Vibrissal follicles in the upper lip from a -day embryo differentiated normally for 4 days in excess vitamin A (12·5 i.u./ml.), and then some follicles became misshapen and developed gland-like lateral buds, while follicles in the control explant continued normal development and produced many keratinized hairs. All the vibrissal follicles originally present in four explants of upper Up from 14-day embryos differentiated normally for about 3 days in excess vitamin A (12·5 i.u./ml.) and then showed metaplastic changes. Many of them underwent a complete glandular metaplasia, being transformed into compound tubular glands with branching duct systems, terminal ‘alveolar’ swellings and occasional signs of mucous secretion. Some follicles retained traces of the original structure, and in a few the follicle eventually recovered its capacity for normal differentiation, producing simultaneously a small keratinized hair and a vigorously growing gland. The metaplastic glands were unlike any normal mammalian skin glands but resembled immature salivary glands. At the time of initiation of the metaplasia there was also an increase in the secretion of sebum or sebum-like material in the same hair follicles. In the control group without excess vitamin A the follicles continued normal differentiation and hair production until the experiment was terminated, and there was no metaplasia. Most of the vibrissal follicles in the explants of upper lip from 15-day embryos continued normal differentiation in the presence of excess vitamin A (12·5 i.u./ml.), although a higher proportion of the hairs were abnormal in structure than in the control group. In excess vitamin A a few of the initially least advanced follicles underwent glandular metaplasia, but no metaplasia was observed in the control group. Some of the differences between the behaviour of explants from embryos of different ages could be explained by the hypothesis that there is only a relatively short critical stage in follicle development during which vitamin A is capable of inducing metaplasia.