Yu Minghui, Ju Haixin, Ye Ningli, Chen Jing, Sun Lei, Wu Xiaohui, Xu Hong, Shen Qian
Department of Nephrology, Children's Hospital of Fudan University, Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.
State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.
Am J Nephrol. 2025;56(2):187-197. doi: 10.1159/000541289. Epub 2024 Sep 23.
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.
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.
We effectively established a prepregnancy vitamin A-deficient mouse model by providing a particular diet with or without vitamin A for 4 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.
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.
在动物模型和人群研究中，孕期维生素A水平适中与正常胚胎发育密切相关。泌尿系统的异常发育与维生素A过量或缺乏有关。受孕前母体维生素A缺乏、孕期适度补充维生素A与后代泌尿系统发育异常之间的关系尚不清楚。
通过建立受孕前和受孕前+孕期维生素A不足的小鼠模型，我们研究了孕期适度补充维生素A是否可以降低先天性肾脏和尿路畸形（CAKUT）的患病率，并提高后代体内维生素A的水平，以及其中涉及的任何潜在途径。
通过提供含或不含维生素A的特定饮食4周，我们有效地建立了受孕前维生素A缺乏的小鼠模型。维生素A缺乏模型组的后代出现新生儿泌尿系统发育畸形的比例更高。输尿管芽出现异常以及肾脏发育过程中的关键分子，如p-Plcγ和Ret，可能是母亲维生素A缺乏导致后代发生CAKUT发育异常的主要原因。另一方面，正常的维生素A饮食可能有助于减轻受孕前维生素A缺乏的致畸后果，以及输尿管芽形成和主要分子变化所产生的缺陷。
相比之下，孕期给予正常的维生素A饲料可能在一定程度上改善受孕前维生素A缺乏的致畸作用，也可能改善与输尿管芽形成和关键分子变化相关的异常情况。
