Fisher M C, Zeisel S H, Mar M H, Sadler T W
Department of Cell Biology and Anatomy, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
Teratology. 2001 Aug;64(2):114-22. doi: 10.1002/tera.1053.
Choline is an essential nutrient in methylation, acetylcholine and phospholipid biosynthesis, and in cell signaling. The demand by an embryo or fetus for choline may place a pregnant woman and, subsequently, the developing conceptus at risk for choline deficiency.
To determine whether a disruption in choline uptake and metabolism results in developmental abnormalities, early somite staged mouse embryos were exposed in vitro to either an inhibitor of choline uptake and metabolism, 2-dimethylaminoethanol (DMAE), or an inhibitor of phosphatidylcholine synthesis, 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH(3)). Cell death following inhibitor exposure was investigated with LysoTracker Red and histology.
Embryos exposed to 250-750 microM DMAE for 26 hr developed craniofacial hypoplasia and open neural tube defects in the forebrain, midbrain, and hindbrain regions. Embryos exposed to 125-275 microM ET-18-OCH(3) exhibited similar defects or expansion of the brain vesicles. ET-18-OCH(3)-affected embryos also had a distended neural tube at the posterior neuropore. Embryonic growth was reduced in embryos treated with either DMAE (375, 500, and 750 microM) or ET-18-OCH(3) (200 and 275 microM). Whole mount staining with LysoTracker Red and histological sections showed increased areas of cell death in embryos treated with 275 microM ET-18-OCH(3) for 6 hr, but there was no evidence of cell death in DMAE-exposed embryos.
Inhibition of choline uptake and metabolism during neurulation results in growth retardation and developmental defects that affect the neural tube and face.
胆碱是甲基化、乙酰胆碱和磷脂生物合成以及细胞信号传导过程中的一种必需营养素。胚胎或胎儿对胆碱的需求可能使孕妇以及随后发育中的胚胎面临胆碱缺乏的风险。
为了确定胆碱摄取和代谢的中断是否会导致发育异常，将早期体节期小鼠胚胎在体外暴露于胆碱摄取和代谢抑制剂2-二甲基氨基乙醇（DMAE）或磷脂酰胆碱合成抑制剂1-O-十八烷基-2-O-甲基-rac-甘油-3-磷酸胆碱（ET-18-OCH(3)）。使用溶酶体追踪红和组织学方法研究抑制剂暴露后的细胞死亡情况。
暴露于250 - 750微摩尔DMAE 26小时的胚胎出现颅面发育不全以及前脑、中脑和后脑区域的开放性神经管缺陷。暴露于125 - 275微摩尔ET-18-OCH(3)的胚胎表现出类似的缺陷或脑泡扩张。受ET-18-OCH(3)影响的胚胎在神经孔后部的神经管也有扩张。用DMAE（375、500和750微摩尔）或ET-18-OCH(3)（200和275微摩尔）处理的胚胎的胚胎生长均受到抑制。用溶酶体追踪红进行整体染色和组织学切片显示，用275微摩尔ET-18-OCH(3)处理6小时的胚胎中细胞死亡区域增加，但在暴露于DMAE的胚胎中没有细胞死亡的证据。
在神经胚形成过程中抑制胆碱摄取和代谢会导致生长迟缓和影响神经管及面部的发育缺陷。
