A fetal mouse model of ventricular non-compaction using retinoic acid

Abstract

ObjectiveTo develop a fetal mouse model of non-compaction of ventricular myocardium (NVM) using All-trans retinoic acid (ATRA). MethodsPregnant mice were divided into blank control group, dimethyl sulfoxide (DMSO) control group and ATRA group. The pregnant mice at 8.5 days after pregnancy were given 70 mg/kg ATRA in DMSO to induce fetal mouse model of NVM in ATRA group. All the hearts were acquired and sliced in short axis from the neonatal mice sacrificed after delivery. Pathological changes were visualized under 40- and 100-fold magnification with Hematoxylin-eosin (HE) staining at different ventricular levels. The criteria for pathological diagnosis of classical NVM were: prominent trabeculations on the endocardial surface and deep intertrabecular recesses communicating with the ventricular cavity and the thickness ratio of non-compacted layer (N) to compact myocardium layer (C) N/C > 1.4. Analysis of variance (ANOVA) and least significant difference (LSD) were used to analyze the differences of three groups, with P < 0.05 considered as significant. ResultsThe typical characteristics of NVM histopathological findings of ATRA fetal mouse were confirmed: compared to the hearts of blank control group (n = 20) and DMSO control group (n = 15), all the hearts of ATRA group (n = 17) showed the obviously thinner compacted layer and the much thicker non-compacted layer. The N/C ratio of left ventricles (LVs) in ATRA group was 2.735 ± 1.634, higher than those in DMSO control group 0.178 ± 0.119 and blank control group 0.195 ± 0.118 with significant difference (F = 32.550, P <0. 0001); N/C ratios of right ventricles (RVs) in the ATRA group were (6.068 ± 4.394), higher than those in the DMSO control group 0.459 ± 0.24 and in the blank control group 0.248 ± 0.182 with significant difference (F = 20.069, P <0.0001). LSD of LVs and RVs showed a significant difference between ATRA and blank control group (P < 0.0001), and between ATRA and DMSO control group (P < 0.0001). LSD showed no significant difference in two control groups of LVs (P = 0.963) and of RVs (P = 0.848) . ConclusionExcess ATRA could be used to induce NVM of fetal mice heart. This animal model might provide a platform for fundamental research of NVM pathogenesis and potential targeting treatment.