Does the developing liver inhibit early lung growth in congenital diaphragmatic hernia?

It has been hypothesised that the liver induces lung hypoplasia in congenit al diaphragmatic hernia (CDH) by non-compressive intrathoracic growth rathe r than traditional mass herniation. Utilising a co-culture system, we teste d the capacity of liver cells to inhibit lung growth by contact rather than compression. Heart, liver, and lungs were microdissected from normal rat e mbryos (n > 20 from at least three litters) on day 13.5 of gestation. Monol ayer cultures of enzymatically dispersed livers and hearts were established at the same cell density. Lung primordia were cultured in direct contact w ith hepatic cells or partitioned from them by a permeable polytetrafluoroet hylene membrane. This permits the contributions of diffusable factors and c ell contact to be distinguished. Lungs were similarly cultured in direct co ntact with or partitioned from cardiac cells. Lungs cultured in isolation s erved as further controls. Daily inspection permitted assessment of in-vitr o lung growth. Growth of lungs in direct contact with hepatic cells was equ ivalent to that of lungs partitioned from liver cells. Lungs in direct cont act with cardiac cells and lungs partitioned from cardiac cells were also n ot inhibited compared to lungs cultured in isolation. Early lung developmen t is thus not inhibited by humoral or contact-mediated interactions with em bryonic liver cells. Lung hypoplasia in CDH is therefore unlikely to origin ate from contact inhibition with the developing Liver. An intrinsic pulmona ry defect may better explain hypoplastic lung development in CDH.