Loo Christine K C, Pearen Michael A, Pereira Tamara N, Perry-Keene Joanna, Payton Diane, Ramm Grant A
Dept of Anatomical Pathology, NSW Health Pathology, Prince of Wales Hospital, Sydney, Australia; Hepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Hepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Early Hum Dev. 2018 Jan;116:17-23. doi: 10.1016/j.earlhumdev.2017.10.005. Epub 2017 Nov 5.
Abnormal retinoic acid (RA) signalling is considered a major cause of congenital diaphragmatic hernia (CDH). Pulmonary hypoplasia and pulmonary hypertension are the major causes of morbidity and mortality in infants born with CDH. Experimental studies in animals have found that RA signalling is involved in lung and liver development, but animal models of CDH do not directly correlate with CDH in human fetuses. This study investigated if RA status is also linked to lung and liver growth in human fetuses with CDH.
Hepatic stellate cells (HSC) in autopsy human fetal liver tissue were identified using cRBP-1 immunohistochemistry and the numbers of HSC manually counted. In mammals, RA is principally stored in HSC complexed to cRBP-1 and therefore cRBP-1 HSC numbers were used as an indicator of fetal RA status. The number of HSCs was correlated with liver and lung weights, calculated relative to either normal biometric values or fetal body weight.
The number of cRBP-1 HSCs correlated with lung weight contralateral to the side of the diaphragmatic hernia (r=0.82, p=0.025) and combined lung weight (r=0.78, p=0.039) but not with ipsilateral lung weight (r=0.43, p=0.33), in fetuses with right and left CDH and a case of giant omphalocoele. Liver growth was influenced by contact with diaphragm but not significantly correlated with cRBP-1 expression (r=0.52, p=0.056).
Fetal RA stores, reflected in the number of cRBP-1 HSCs, influence lung growth as well as diaphragm development in human fetuses with CDH. Contact with diaphragm influenced liver growth.
