Vitamin A deficiency disturbs Ret expression and induces urinary tract developmental abnormalities in mice

Abstract

Introduction: Moderate vitamin A levels during pregnancy are strongly related to normal embryonic development in both animal models and population studies. Abnormal development of urinary tract system is linked to either an excess or a shortage of vitamin A. The relationships among maternal vitamin A deficiency prior to conception, moderate vitamin A supplementation during pregnancy, and abnormal urinary system development in offspring are unclear. Methods: By creating preconception and preconception + pregnancy vitamin A insufficiency mouse models, we investigated whether moderate vitamin A treatment during pregnancy may reduce the prevalence of CAKUT and increase distant vitamin A levels in offspring, as well as any potential pathways involved. Results: We effectively established a prepregnancy vitamin A-deficient mouse model by providing a particular diet with or without vitamin A for four weeks. The offspring of the hypovitaminosis A model group presented a greater proportion of neonatal urinary tract developmental malformations. Abnormalities in ureteral bud emergence and key molecules during renal development, such as p-Plcγ and Ret, may be the primary causes of offspring development of CAKUT as a result of mothers’ hypovitaminosis A. Normal vitamin A diets, on the other hand, may help mitigate the teratogenic consequences of prepregnancy hypovitaminosis A, as well as defects produced by ureteral budding and major molecular changes. Conclusion: In contrast, the administration of normal vitamin A feeds during pregnancy may ameliorate the teratogenic effects of prepregnancy hypovitaminosis A to a certain extent and may also ameliorate the abnormalities associated with ureteral budding and key molecular changes.