Universidad Complutense de Madrid, Faculty of Optics and Optometry, Anatomy and Embryology Department, Madrid, Spain.
Universidad Complutense de Madrid, Faculty of Optics and Optometry, Anatomy and Embryology Department, Madrid, Spain; Universidad Complutense de Madrid, Faculty of Medicine, Anatomy and Embryology Department, Madrid, Spain.
Nutrition. 2021 Oct;90:111250. doi: 10.1016/j.nut.2021.111250. Epub 2021 Mar 26.
Folic acid (FA) is crucial before and during early pregnancy. FA deficiency can occur because dietary FA intake is low in mothers at the time of conception. Likewise, various ocular pathologies are related to the alteration of extracellular matrices. The present study aimed to investigate the association between maternal FA deficiency and congenital eye defects. We also investigated whether maternal diet deficient in FA alters the expression of collagen IV and laminin-1 as a possible mechanism responsible for the appearance of ocular malformations. Both proteins are the main components of the basal lamina, and form an interlaced network that creates a relevant scaffold basement membrane. Basal laminae are involved in tissues maintenance and implicated in regulating many cellular processes.
A total of 57 mouse embryos were classified into the following groups: Control group, (mothers were fed a standard rodent diet), and D2 and D8 groups (mothers were fed FA-deficient [FAD] diet for 2 or 8 wk, respectively). Female mice from group D2 were fed a FAD diet (0 mg/kg diet + 1% succinyl sulfathiazole used to block the synthesis of FA) for 2 wk from the day after mating until day 14.5 of gestation (E14.5). On the other hand, female mice from group D8 were fed a FAD diet for 8 wk (6 wk before conception and during the first 2 wk of pregnancy). For the data analysis, we first estimated the incidence of malformations in each group. Then, the statistical analysis was performed using IBM SPSS Statistics, version 25.0. Expression patterns of collagen IV and laminin-1 were examined with the immunohistochemical technique.
Our results showed that mice born to FA-deficient mothers had several congenital eye abnormalities. Embryos from dams fed a short-term FAD diet were found to have many significant abnormalities in both anterior and posterior segments, as well as choroidal vessel abnormalities. However, embryos from dams fed a long-term FAD diet had a significantly higher incidence of eye defects. Finally, maternal FA deficiency increased the expression of both collagen IV and laminin-1. Likewise, changes in the spatial localization and organization of collagen IV were observed.
A maternal FAD diet for a short-term period causes eye developmental defects and induces overexpression of both collagen IV and laminin-1. The malformations observed are probably related to alterations in the expression of basement membrane proteins.
叶酸（FA）在妊娠前和妊娠早期至关重要。由于受孕时母亲的饮食 FA 摄入量低，可能会出现 FA 缺乏。同样，各种眼部病变与细胞外基质的改变有关。本研究旨在探讨母体 FA 缺乏与先天性眼部缺陷之间的关系。我们还研究了母体 FA 缺乏饮食是否会改变胶原蛋白 IV 和层粘连蛋白-1 的表达，作为导致眼部畸形出现的可能机制。这两种蛋白质都是基底膜的主要成分，形成相互交织的网络，构成相关的基底膜支架。基底膜参与组织维持，并参与调节许多细胞过程。
将 57 只小鼠胚胎分为以下几组：对照组（母亲喂食标准啮齿动物饮食）和 D2 组和 D8 组（母亲分别喂食 FA 缺乏[FAD]饮食 2 或 8 周）。D2 组的雌性小鼠从交配后的第二天到妊娠第 14.5 天（E14.5）喂食 FAD 饮食（0mg/kg 饮食+1%琥珀酰磺胺噻唑用于阻断 FA 的合成）2 周。另一方面，D8 组的雌性小鼠喂食 FAD 饮食 8 周（受孕前 6 周和妊娠的前 2 周）。对于数据分析，我们首先估计每组畸形的发生率。然后，使用 IBM SPSS Statistics 版本 25.0 进行统计分析。使用免疫组织化学技术检查胶原蛋白 IV 和层粘连蛋白-1 的表达模式。
我们的结果表明，FA 缺乏的母亲所生的小鼠有多种先天性眼部异常。喂食短期 FAD 饮食的胚胎在前部和后部以及脉络膜血管均发现许多明显异常，但喂食长期 FAD 饮食的胚胎眼部缺陷发生率明显更高。最后，母体 FA 缺乏增加了胶原蛋白 IV 和层粘连蛋白-1 的表达。同样，观察到胶原蛋白 IV 的空间定位和组织变化。
短期母体 FAD 饮食会导致眼部发育缺陷，并诱导胶原蛋白 IV 和层粘连蛋白-1 的过度表达。观察到的畸形可能与基底膜蛋白表达的改变有关。
