Effect of gas composition on liquid secretion by explants of distal lung of fetal rat in submersion culture

Abstract

Throughout gestation, fetal lung is filled with liquid secreted by the pulmonary epithelium. Factors responsible for secretion and for induction of liquid absorption by postnatal lung are poorly understood. We studied effects of “fetal” (3% O2-8% CO2) and “postnatal” (21% O2-5% CO2) gas tensions and of low hormone concentrations [media with 10% charcoal-stripped fetal bovine serum (stFBS) or unstripped FBS] on water content and morphology of distal lung explanted from 14-, 20-, and 22-day fetal (term, 22 days) and 2-day neonatal rats and incubated in submersion culture. Water-to-dry weight ratios of freshly excised fetal whole lung at 20 (6.2) or 22 days (7.0) were greater than that of 2-day postnatal lung (4.7). Culture conditions did not affect water-to-dry weight ratio of cyst-forming 14-day explants (10.8) or acystic 2-day postnatal explants (2.4). Fetal gases and stFBS supported cyst formation in [and high water/dry weight (9.2, 12.6) of] 20- and 22-day explants. Cysts also formed in 20-day explants exposed to postnatal gases and stFBS (water/dry weight = 6.5). Other conditions resulted in minimal cyst formation by 20- and 22-day explants and in water/dry weight similar to that of freshly excised and drained distal lung from 22-day fetuses (2.1). Cysts were lined with cuboidal and thin epithelial cells. No cells were ciliated. We conclude that 1) secretion dominates liquid flow across epithelia of fetal rat lung until birth, 2) alveolar epithelium contributes to this secretion, and 3) liquid secretion by fetal distal lung late in gestation is regulated by gas composition.