EPIDERMAL BARRIER ONTOGENY - MATURATION IN SERUM-FREE MEDIA AND ACCELERATION BY GLUCOCORTICOIDS AND THYROID-HORMONE BUT NOT SELECTED GROWTH-FACTORS

Because the cutaneous permeability barrier develops late in gestation, prematurity may result in increased morbidity and mortality due to ba rrier incompetence, The purpose of the present study was to develop an in vitro model of barrier ontogenesis in order to identify those fact ors critical for fetal barrier formation, Skin explants from gestation al day 17 fetal rats (term is 22 days) were incubated in hormone- and serum-free media, After 4 d in culture, a multi-layered stratum corneu m (SC) developed that demonstrated a membrane pattern of fluorescence using the hydrophobic probe, nile red, and the deposition of mature la mellar unit structures throughout the SC interstices, ultrastructurall y. Transepidermal water loss rates declined during explant culture suc h that after 4 d a competent barrier was present, Similarly, lanthanum permeation studies showed tracer penetration into all cell layers exp lants, whereas it did not penetrate above stratum granulosum in 4-d ex plants, Thus, the chronology of epidermal development in the explants precisely mirrored that observed in utero. Treatment with either 10 nM dexamethasone or 10 nM triiodothyronine accelerated SC development an d barrier formation by 2 d, These results indicate that (i) the late e vents of fetal epidermal development progress in vitro under serum- an d growth factor-free conditions, culminating in the formation of a fun ctional barrier, and (ii) both dexamethasone and triiodothyronine acce lerate barrier development.