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The permeability of the skin of fetal rats between 14 and 21 days of intrauterine life was investigated by injecting lanthanum nitrate solution subepidermally and by exposing the external surface of other fetuses to the same solution. Up to the age of 18 days, the epidermis was freely permeable from the basal surface and lanthanum entered junctional complexes between periderm cells. After 18 days, the limit of permeation corresponded to the level at which membrane-coating granules were released into the intercellular spaces. At all ages, permeation from the outer surface was limited to the junctional complexes between the periderm cells covering the epidermis throughout fetal life. Damage to the periderm at early ages resulted in complete penetration of the epidermis by lanthanum. It was concluded that, prior to secretion of the epidermal permeability barrier at 18 days, the periderm was the principal barrier to permeation by lanthanum.

In the ventral epidermis of fetal rats the size and distribution of intercellular gap junctions changed during differentiation. In the young fetus, between 13 and 17 days, large gap junctions sometimes exceeding 3 micron in profile length were found predominantly in basal cells. As the epidermis increased in thickness the mean profile length diminished until only small gap junctions were present mainly in more superficial layers even persisting into the stratum corneum. Endocytosis of the intercellular gap junctions gave rise to intracytoplasmic annular gap junctions (AGJs) which occurred after 17 days predominantly in the superficial three layers of the epidermis. The AGJs diminished in mean diameter with the age of the fetuses possibly as a consequence of the decreasing size of the intercellular gap junctions from which they had formed. Rarely sequestration of AGJs by cytoplasmic membranes occurred but many recognizable AGJs persisted into the stratum corneum. As in other developing systems, the function of gap junctions in epidermis is unknown but the extensive junctions of younger epidermis might be related to the maintenance of a greater level of uniformity both of mitotic activity and of differentiation.

Membrane-coating granules of the epithelium of the hamster cheek pouch displayed a lamellated internal structure consisting of alternating thick and thin electron dense bands separated by translucent bands of equal width. The repeat distance of the contents was 8.5 nm +/- sd. 0.7 nm and the thickness of the major electron dense band was 3 nm +/- sd 0.4 nm. After exocytosis from the cells the lamellated material became organised into extensive sheets and the dimensions changed so that the repeat distance was 10.9 nm +/- sd 0.6 nm but the major electron dense band was virtually unchanged at 3.33 nm +/- sd 1.1 nm. The narrower or intermediate dense band became progressively less easy to see and was virtually invisible at the surface of the epithelium. It is suggested that the changes observed may be due to an increase in hydration of a phospholipid/protein complex in the granules by permeaton of water along the intermediate dense band.

The sequence of events in the establishment of a keratinised epidermis has been related to age and crown rump length in fetal rats. Differentiation of the epidermis occurs under cover of the periderm throughout gestation. Ten stages are defined between 12d intra-uterine life and birth. Membrane-coating granules (MCGs) appeared at 18d (Stage 4) after the appearance of tonofilaments but before the appearance of the first "fetal" keratohyaline granules (KHGs) at 19d (Stage 5). Measurement of the position of MCGs within the cells showed a less marked concentration near the superficial border of the cells than that found at later stages. As KHGs formed, exocytosis of MCGs occurred into the intercellular space immediately deep to the periderm. It is suggested that after 19d (Stage 5) the periderm serves to retain the contents of the MCGs in this space so providing the permeability barrier and that prior to that stage the periderm itself probably provides the permeability barrier of fetal skin.

An electron-dense tracer (Thorotrast) was injected into the lamina propria of the keratinized epithelium of the buccal mucosa of rats. Electron microscopy showed that it crossed the basal lamina and penetrated the intercellular spaces of the epithelium up to the proximal layers of the stratum granulosum. Thorotrast was ingested by the epithelial cells in the stratum basale and stratum spinosum and localized in large vesicles and eventually in the membrane-coating granules. The latter, already known to contain lysosomal enzymes, are therefore to be regarded as secondary lysosomes formed in part as a sequel of endocytosis in deeper cell layers. The postulated origin of MCGs directly from the Golgi apparatus is rendered less likely by this observation. Thorotrast remaining in the cells when keratinization is completed is either dispersed into the cytoplasm or else incorporated into keratohyalin granules.