ONTOGENY OF APOPTOSIS DURING LUNG DEVELOPMENT

Apoptosis has been shown to be involved in several processes during em bryogenesis, but the ontogeny of apoptosis during lung development has not been studied. The goals of the current study were to determine if apoptosis occurs during lung development, and to determine the ontoge ny of the changes in apoptosis that occur. We studied the ontogeny of apoptosis in vivo using lungs from 14-18-d gestation fetal rats, newbo rn rats, and 1-d-, 2-d-, 5-d-, and 10-d-old rat pups. Apoptosis was as sessed by electron microscopy and the terminal deoxyribonucleotidyl tr ansferase dUTP nick end-labeling assay. We compared the in vivo result s with explants of 14-d gestation fetal rat lung placed in culture for 1-4 d because the biochemical development of the lung in organ cultur e has been shown to closely parallel the development of the lung in vi vo. We found apoptosis of mesenchymal cells at the periphery of distal lung buds in early fetal lung (14-16-d gestation). Apoptosis of both mesenchyme and epithelium was present in later fetal lung (18-d gestat ion). There were no qualitative differences in apoptosis between in vi vo fetal lung and explant cultures of fetal lung. There was a 14-fold increase in apoptosis at birth and in the first postnatal day of life (9-12% of cells) compared with fetal lung (0.6-1% of cells). This was followed by a rapid decline in the percentage of apoptotic cells to fe tal levels at postnatal d 2-10. We conclude that apoptosis occurs in a spatially, temporally, and cell-specific manner during lung developme nt. The number of cells undergoing apoptosis increases dramatically in the first day after birth.