Liver pathological alterations in fetal rabbit model of congenital diaphragmatic hernia

Abstract

To date, fetal liver implication is not a well-understood phenomenon in congenital diaphragmatic hernia (CDH). We evaluated the fetal morphologic changes on liver growth after surgical procedure in CDH experimental model. A diaphragmatic defect at gestational day E25 and tracheal occlusion (TO) at E27 were surgically created in rabbit fetuses. Five experimental groups were assessed: control group, left CDH, right CDH, CDH + TO, and TO alone. Body and organ growth were measured. For histological evaluation of the CDH effect, liver sections were collected. Left-CDH group had livers with increased leukocyte infiltration in comparison with controls (p = 0.02). Increased capillary sinusoid congestion and hepatocyte vacuolation were greater in left-CDH compared with the right-CDH group (p = 0.05). Capillary sinusoid congestion and interstitial edema were more evident in the left-CDH compared with CDH + TO group (p = 0.05). Increases in sinusoid congestion, hepatocyte vacuolation, and interstitial edema were also greater in the CDH + TO compared with controls (p ≤ 0.02). Intrathoracic liver weight was higher in right-CDH compared with left-CDH group (p < 0.001). Total lung weights (TLW) were significantly lower in both left-CDH compared with controls (p < 0.001), CDH + TO (p = 0.01), and TO (p < 0.01) and in right-CDH compared with CDH + TO (p < 0.01) and TO (p < 0.01).Decreased kidney and heart weights were also recorded. Hemodynamics and structural fetal liver changes in laterality were noted in CDH model. Regulation of intrathoracic liver weights seems to be disturbed by the absence of diaphragmic contact.Pulmonary injury is supported by the effect of a first hit, while the growth of internal organs suggests a multisystemic remodeling related to the fetal adaptation.

The interplay between prenatal liver growth and lung development in congenital diaphragmatic hernia

“…Additionally, liver growth is greater below when compared to above the diaphragm. This finding parallels findings from a recent study in a fetal rabbit model of CDH ( 30 ). The authors found that the intra-thoracic liver weight was higher in right-sided CDH ( 30 ).…”

“…This finding parallels findings from a recent study in a fetal rabbit model of CDH ( 30 ). The authors found that the intra-thoracic liver weight was higher in right-sided CDH ( 30 ). They also showed that there was corresponding lower lung weight in both left- and right-sided CDH when the liver was growing in the chest ( 30 ).…”

“…The authors found that the intra-thoracic liver weight was higher in right-sided CDH ( 30 ). They also showed that there was corresponding lower lung weight in both left- and right-sided CDH when the liver was growing in the chest ( 30 ). The authors postulated that these differences could be due to lower compartmental pressures when the defect is directly over the liver allowing for increasing liver growth.…”