Immaturity of the epidermal barrier in the preterm infant may have ser
ious clinical consequences. However, regardless of the degree of prema
turity, the barrier rapidly matures such that by 2 wk all infants disp
lay a competent barrier. To determine whether the change from an aqueo
us (intrauterine) to a xeric environment might be the stimulus for thi
s accelerated maturation, we examined the effects of air exposure on c
utaneous barrier formation in vitro. Skin explants from d 17 fetal rat
s were incubated either submerged or at the air-medium interface. As p
reviously reported, a competent barrier formed under submerged conditi
ons after 3-4 d, precisely mirroring the time course of maturation in
utero. In contrast, barrier maturation was accelerated in air-exposed
explants, with functional, histologic, and structural markers of barri
er formation observed after only 2 d of incubation. A water-impermeabl
e membrane blocked the acceleration of barrier formation, resulting in
a developmental time course comparable to that for submerged explants
. In contrast, a water vapor-permeable membrane did not block the acce
leration. Glucocorticoids and thyroid hormone, which accelerate barrie
r formation in utero or in vitro under submerged conditions, did not f
urther accelerate barrier formation in the air-exposed model. These da
ta indicate that: I) air exposure accelerates barrier ontogenesis, sug
gesting that water flux may be an important signal for the accelerated
barrier formation that occurs in premature infants; and 2) factors wh
ich accelerate barrier formation in utero may not further accelerate b
arrier formation in neonates.