Retinoic acid treatment partially rescues failed septation in rats and in mice

TLDR

Pulmonary alveoli arise through septation of immature lung sacs, and when this process fails, no spontaneous post‑hoc septation occurs and no method has yet been shown to induce it. The study tested whether all‑trans retinoic acid can trigger post‑hoc septation. Researchers quantified lung volume, individual alveolar volume, surface area, and calculated alveolar number in neonatal rats with glucocorticosteroid‑blocked septation and adult tight‑skin mice with a genetic septation defect. All‑trans retinoic acid induced post‑hoc septation in both species and developmental stages, indicating a potential therapeutic approach for premature infants.

Abstract

Pulmonary alveoli are formed in part by subdivision (septation) of the gas-exchange saccules of the immature lung. Septation results in smaller, more numerous structures (alveoli) and is developmentally regulated in mammals including humans, rats, and mice; if it fails to occur at the appropriate time, there is no spontaneous post hoc septation nor has there been a means of inducing septation after it has failed to occur. We measured lung volume, the volume of individual alveoli, and alveolar surface area and calculated alveolar number in neonatal rats in which septation had been blocked by treatment with a glucocorticosteroid hormone and in adult tight-skin mice that have a genetic failure of septation. We tested the hypothesis that treatment with all- trans retinoic acid induces post hoc septation. In both models of failed septation, hence in two species, and in immature and adult animals, treatment with all- trans retinoic acid induced post hoc septation, offering the possibility of a similar effect in premature infants.