FETAL EPIDERMIS 135 of the participation of the epidermal --SH in the development of the pilary system, which is essentially completed at birth in the guinea pig, while it is still in progress during the neonatal period in the rat. Dynamics of Barrier Formation In the guinea pig fetus, the fully-matured barrier formed during the last 10-11 days of gestation, in reasonable agreement with the reported turnover time of adult guinea pig epidermis of 8.5 days (20). In a semilogarithmic plot of the water diffusion rate vs. time (day of gestation), the slope of the line expresses the rate of genesis of the per- meability barrier. In the fetal guinea pig a uniform rate of barrier de- velopment is seen, unlike the biphasic recovery reported by others (21- 23) following removal of the outer layers of human skin by tape strip- ping. If one plots Matoltsy's data on stripped skin (21) on a semilogarith- mic scale, both phases tend to be linear, the initial rapid period with a slope of 0.3, the second slower phase with a slope of 0.1. The slope char- acterizing barrier formation in the fetal guinea pig is 0.11, indicating that the kinetics of barrier formation under fetal conditions are similar to those for regeneration of the normal barrier following its mechanical removal. Sulfhy dry l C hanges While there seems to be some direct relation between epidermal levels and the development of a functional skin barrier, there is evidence from other sources that this may not be involved with the formation of disulfide linkages. Matoltsy et al. (24) found that reagents capable of cleaving disulfide tinkages have a relatively small effect on barrier per- meability, and even the widely-held notion that the genesis of disulfide linkages is the definitive event in keratinization has been seriously ques- tioned (16, 25). It would be of considerable interest to know whether the increased sulfur metabolism seen in the final stages of barrier formation in the fetus also occurs in postnatal life on recovery from barrier damage fol- lowing an insult such as Scotch-tape stripping of the skin surface layers. It would also be of value to know whether a disturbance of the sulfur metabolism in the skin (26) is in any way involved in the etiology of com- mon skin disorders such as psoriasis in which there is a deficient barrier function resulting from a disturbed keratinization process.

136 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS SUMMARY The ultrastructure, sulfhydryl content, and water permeability of the epidermis were studied in the fetal rat and guinea pig. The results indi- cated: 1. Barrier development occurred during the final quarter of gestation and was essentially complete at term. The kinetics of barrier formation in the fetal guinea pig were similar to those reported for cell renewal in adult guinea pigs and for the final phase of barrier regeneration following tape-stripping of human skin. 2. The outstanding structural changes associated with barrier devel- opment in the fetus involved increasing intercellular cohesion, the ag- gregation of tonofilaments into well-defined bundles, and the appear- ance and subsequent differentiation of the granulosum giving rise to the stratum corneum. Thus the barrier, fully matured as determined in water permeability studies, is associated only with fetal skin showing a completely keratinized horny layer. 3. In the earlier stages of barrier development, there is a marked in- crease in the levels of sulfhydryl-rich protein in the epidermis. A peak sul•hydryl level which represented approximately 20 times the amount normally present in adult epidermis was found just before parturition. The sulfhydryl level then fell as rapidly as it had increased. While some of the sulfhydryl undoubtedly was oxidized to form interchain disulfide bonds, it is suspected that sulfhydryl participates in some other way in the formation of the skin barrier. At term, a relatively large amount of sulfhydryl still was in the reduced state. (Received June 18, 1970) REFERENCES (1) Vinson, L. J., Singer, E. J., Koehler, W. R., Lehman, M.D., and Masurat, T., The nature of the epidermal barrier and some factors influencing skin permeability, Toxicol. Appl. Pharmacol., 7, suppl. 2, 7 (1965). (2) Manual [or Laboratory Animal Care, Sect. I: Introduction to Laboratory Animals, Ralston Purina Co., St. Louis, Mo., 1961. (3) Altman, P. L., and Dittmer, D. S., Growth, Including Reproduction and Morphological Development, Fed. Amer. Soc. Exp. Biol., Washington, D.C., 1962. (4) Gruneberg, H., The development of some external features in •nouse embryos, ]. Hered., 34, 88-92 (1943). (5) Burch, G. E., and ¾¾insor, T., Diffusion of water through dead plantar, pahnar and torsal human skin and through toe nails, Arch. Dermatol. Syphilol., 53, 39 (1946). (6) Barrnett, R. J., and Seligman, A.M., Histochemical demonstration of protein-bound sulfhydryl groups, Science, 1115, 323 (1952).