ABSTRACT:The fetal epidermal barrier undergoes rapid development during late gestation despite conditions injurious to the skin postnatally, i.e. prolonged exposure to water (urine) and noxious substances such as pancreatic chymotrypsin. Nevertheless, at birth, term newborns have a superb epidermal barrier. Concomitant with formation of the stratum corneum in utero, vernix caseosa forms a natural multifunctional cream separating the skin surface from the amniotic fluid with possible unique barrier properties. Therefore, we investigated the effect of native vernix, synthetic vernix, and Desitin ® on penetration of chymotrypsin, a proteolytic enzyme present in both developing epidermis and meconium. ␣-Chymotrypsin penetration through test materials was conducted in vitro using a modified Franz diffusion cell. The presence of ␣-chymotrypsin in vernix and a possible inhibitory effect of vernix on ␣-chymotrypsin activity were investigated. Vernix films significantly impeded chymotrypsin penetration compared with controls during 24-h exposure experiments. ␣-Chymotryptic activity in vernix was undetectable, and vernix showed no endogenous inhibition of such activity. Both synthetic vernix and Desitin ® significantly impeded ␣-chymotrypsin penetration compared with controls during 9-h exposure experiments. With respect to the developing epidermal barrier, these results are consistent with the hypothesis that vernix films retain endogenous (epidermal) chymotrypsin while preventing exposure to exogenous (pancreatic) chymotrypsin. T he intrauterine development of the human skin barrier as an interface between the internal and external environment is critical for postnatal survival of the organism. One of the most striking changes during late gestation of pregnancy is the presence of vernix caseosa on the fetal skin surface. Vernix is a viscous, whitish, pastelike material that overlies the fetal stratum corneum (1). By composition, vernix is mainly composed of water (80%), lipid (10.3%), and protein (9.1%) (2). It consists of a lipid matrix containing detached corneocytes derived from possible remnants of the epitrichium, the differentiating fetal epidermis, and the pilosebaceous unit (3,4). Vernix lipid is, thus, composed of two types of lipid: sebaceous lipid and stratum corneum lipid (5-8). The continuous (nonlamellar) phase of vernix lipid surrounding the cellular components has a low surface energy and results in a highly unwettable material located at the fetal skin surface (9). This interfacial hydrophobic material has been investigated as a defense against infection both pre-and postnatally with beneficial physicochemical properties providing barrier protection and facilitating development of the acid mantle (10 -12).Paradoxically, the fetal skin barrier undergoes rapid development during late gestation under conditions of total immersion in amniotic fluid. In vitro, skin culturists must raise human skin to an air interface to promote barrier development (13,14). This raises the biologic question of how the human f...