Programmed cell death in normal fetal rat lung development

Lung development is a coordinated process regulated by the interactions of extracellular and intracellular factors, yet little is known about the proc ess of programmed cell death during lung development. To study this questio n, we examined fetal rat lung from the pseudoglandular period (gestational day 15) to the day of birth (gestational day 21) using BrdU incorporation i nto DMA as a proliferative marker, while in parallel examining several mark ers of programmed cell death including terminal deoxynucleotidyl transferas e-mediated dUTP nick end labeling (TUNEL), DNA "laddering," and expression of programmed cell death pathway proteins. Cell proliferation was ongoing t hroughout fetal days 15 to 21 with a decrease in proliferation over days 20 and 21. Programmed cell death in fetal lung also appeared to be present at all ages examined, but demonstrated 2 peaks of activity at fetal days 15 a nd 18 to 20. Bcl-X-L expression was detected on fetal days 15 to 21, with d iminished expression on days E15 to E18. Cleaved poly(ADP-ribose)polymerase (PARP), activated caspase-3, Bax, and Bad were increased on days 18 to 20. We conclude that proliferation is the primary process driving fetal lung d evelopment with programmed cell death occurring throughout the lung develop mental process to refine structural remodeling.