A Fetal Rat Model of Ventricular Non-compaction Caused by Intrauterine Hyperglycemia.

BACKGROUND: This study aims to develop a fetal rat model of ventricular non-compaction (NVM) using streptozotocin (STZ)-induced gestational hyperglycemia and compare it with a retinoic acid (RA) model.

METHODS: Female SD rats were categorized into STZ, RA, and normal control (NC) groups. The STZ group was given a high-fat diet pre-pregnancy and 35 mg/kg of 2% STZ post-pregnancy. The RA group received a 90 mg/kg dose of RA on day 13 post-pregnancy. Embryonic myocardial morphology was analyzed through HE staining, and embryonic cardiomyocyte ultrastructures were studied using electron microscopy. Diagnoses of NVM were based on a ratio of non-compact myocardium (N) to compact myocardium (C) >1.4, accompanied by thick myocardial trabeculae and a thin myocardial compaction layer. Kruskal-Wallis test determined N/C ratio differences among groups.

RESULTS: Both STZ and RA groups displayed significant NVM characteristics. The left ventricular (LV) N/C in the STZ, RA, and NC groups were 1.983 (1.423-3.527), 1.640 (1.197-2.895), and 0.927 (0.806-1.087), respectively, with a statistically significant difference (P<0.001). The right ventricular (RV) N/C in the STZ, RA, and NC groups were 2.097 (1.364-3.081), 1.897 (1.337-2.662), and 0.869 (0.732-1.022), respectively, with a significant difference (P<0.001). Electron microscopy highlighted marked endoplasmic reticulum swelling in embryonic cardiomyocytes from both STZ and RA groups.

CONCLUSION: Our model underscores the pivotal role of an adverse intrauterine developmental environment in the onset of NVM. This insight holds significant implications for future studies exploring the pathogenesis of NVM.