Epidermal barrier ontogenesis: 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 barrier incompetence. The purpose of the present study was to develop an in vitro model of barrier ontogenesis in order to identify those factors critical for fetal barrier formation. Skin explants from gestational 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 corneum (SC) developed that demonstrated a membrane pattern of fluorescence using the hydrophobic probe, nile red, and the deposition of mature lamellar unit structures throughout the SC interstices, ultrastructurally. Transepidermal water loss rates declined during explant culture such that after 4 d a competent barrier was present. Similarly, lanthanum permeation studies showed tracer penetration into all cell layers in 2-d explants, whereas it did not penetrate above the stratum granulosum in 4-d explants. 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 and barrier formation by 2 d. These results indicate that (i) the late events of fetal epidermal development progress in vitro under serum- and growth factor-free conditions, culminating in the formation of a functional barrier, and (ii) both dexamethasone and triiodothyronine accelerate barrier development.
Hanley
K
K
Department of Dermatology, University of California, San Francisco, USA.
Rassner
U
U
Elias
P M
PM
Williams
M L
ML
Feingold
K R
KR
D000818:Animals; D016895:Culture Media, Serum-Free; D003907:Dexamethasone / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology; D066298:In Vitro Techniques; D008854:Microscopy, Electron; D010539:Permeability / Q000187:drug effects; D051381:Rats; D012867:Skin / Q000187:drug effects* / Q000196:embryology* / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*; D014867:Water / Q000378:metabolism
D016895:Culture Media, Serum-Free; D006133:Growth Substances; D014867:Water; D014284:Triiodothyronine; D003907:Dexamethasone