Retinoic acid receptor-alpha regulates pulmonary alveolus formation in mice after, but not during, perinatal period.

The formation of pulmonary alveoli in mice and rats by subdivision of alveolar saccules that constitute the newborn's gas-exchange region ends by approximately postnatal day 14. However, alveoli continue to form after age 14 days until age approximately 40 days by means other than septation of the saccules present at birth. With the use of morphometric procedures and retinoic acid receptor (RAR)-alpha+/+ and RAR-alpha-/- mice, we now show the volume of individual alveoli (va), the number of alveoli (Na), and alveolar surface area (Sa) are the same in 14-day-old RAR-alpha+/+ and RAR-alpha-/- mice. However, at age 50 days, va is larger, and Na and Sa are smaller, in RAR-alpha-/- than in RAR-alpha+/+ mice, although total lung volume is the same in both groups. These findings, and prior data showing RAR-beta is an endogenous inhibitor of alveolus formation during, but not after, the perinatal period, indicate there are developmental period-specific regulators of alveolus formation and that total lung volume and alveolar dimensions may have different regulators.