Congenital diaphragmatic hernia (CDH) leads to profound and often fatal pulmonary hypoplasia. However the mechanism by which growth is inhibited at a cellular level is not known. The epidermal growth factor family is believed to have a significant role in fetal lung growth. We investigated whether alterations in expression in this growth factor family may play a role in pulmonary hypoplasia in CDH. We used a fetal rat model of CDH induced by administering 2,4, dichlorophenyl-p-nitrophenyl ether (Nitrofen) to 7 pregnant rat mothers on day 11 of a 21 day gestation. The lungs were harvested on day 21 and compared to littermates without CDH. We performed RT-PCR on the mRNA of the CDH and non-CDH lungs for epidermal growth factor (EGF), transforming growth factor α (TGFα), and their receptor, epidermal growth factor receptor (EGFR). The PCR bands were normalized to β actin PCR bands and converted to densitometric units. The data are mean±s.e.m. and were compared by paired t-tests.
We conclude that in this CDH model of pulmonary hypoplasia, on 21 of fetal life, mRNA expression of EGF and its receptor EGFR per lung is not significantly decreased. In contrast there is a significant decrease in the mRNA expression of TGFα per lung, suggesting that this growth factor may have a role in the diminished lung growth seen in CDH. In contrast to the results reported here, we have previously shown in pulmonary hypoplasia due to oligohydramnios that mRNA expression of EGF is significantly decreased, while the mRNA expression of TGFα is significantly increased on day 21 of gestation. Our present findings in this CDH model would indicate that epidermal growth factor and transforming growth factor α have differing roles in the etiology of pulmonary hypoplasia in these two models of altered fetal lung growth. Table
(Spon by: Dale C. Alverson)
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Savich, R., Cummings, C. Alterations in the mRNA Expression of the Epidermal Growth Factor Family in Congenital Diaphragmatic Hernia 304. Pediatr Res 43, 54 (1998). https://doi.org/10.1203/00006450-199804001-00325