ONTOGENY OF THE EPIDERMAL BARRIER TO WATER-LOSS IN THE RAT - CORRELATION OF FUNCTION WITH STRATUM-CORNEUM STRUCTURE AND LIPID-CONTENT

The mammalian epidermal permeability barrier is provided by highly hyd rophobic lipids forming multiple membrane bilayers within the extracel lular domains of the outer, cornified cell layers. To characterize the critical events associated with barrier maturation, we correlated the emergence of a competent barrier to transepidermal water loss with de velopment of the lamellar body secretory system, the organization of s tratum corneum membrane bilayers, and the lipid composition of these m embranes in the perinatal rat. Whereas pups of 19 d estimated gestatio nal age had no measurable barrier (transepidermal water loss > 10 mg/c m2/h), by 21 d the barrier was well established (mean transepidermal w ater loss 0.41 mg/cm2/h). Development of a functional barrier correlat ed with increasing thickness of the stratum corneum, as well as with d evelopment of a membrane pattern of lipid deposition, visualized with the hydrophobic fluorescent probe nile red. At 19 d estimated gestatio nal age, the stratum corneum intercellular domains exhibited an abunda nce of secreted lamellar body contents, but they were not organized in to basic bilayer unit structures. Lamellar unit structures became evid ent by 20 d and extended throughout the stratum corneum interstices by 22 d (term). The quantity of lipid in isolated stratum corneum increa sed significantly between 19 and 20 d (34.08 versus 50.08 mean mu-g li pid/cm2, respectively; p < 0.02) and still further between 20 and 21 d estimated gestational age (74.49-mu-g lipid/cm2; p < 0.001). This inc rease was due to progressive accumulation of neutral lipids, particula rly cholesterol, as well as nonpolar ceramides, as shown by thin-layer chromatography/scanning densitometry. These studies imply that in the development of cutaneous barrier function in the fetal rat both the g eneration of sufficient quantities of hydrophobic lipids and the organ ization of these lipids into bilayer unit structures are required.