Fawcett L B, Pugarelli J E, Brent R L
Department of Pediatrics, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.
Teratology. 2000 May;61(5):332-41. doi: 10.1002/(SICI)1096-9926(200005)61:5<332::AID-TERA4>3.0.CO;2-D.
Heterologous antiserum to the visceral yolk sac (AVYS) is teratogenic, inducing a spectrum of malformations in vivo and producing similar effects in vitro. Numerous studies support the concept that AVYS-induced malformations result from embryonic nutritional deficiency, without affecting the maternal nutritional status. This has provided a useful model with which to investigate the nutritional requirements of the early embryo, as well as the role of various nutrients in the etiology of congenital defects.
In the current investigation, we examined the effects of methionine and other nutrients on AVYS-induced embryotoxicity in vitro. For these experiments, we cultured rat embryos (9.5 p.c) for 48 hr with AVYS and/or methionine at several concentration levels.
The addition of L-methionine to AVYS-exposed cultures reduced dysmorphology and open neural tube; this effect was concentration dependent. AVYS-induced dysmorphology was completely prevented at a concentration of L-methionine corresponding to 50-fold the basal serum concentration. Utilization of D-methionine, L-leucine, or folic acid (5-methyltetrahydrofolate, MTHF) instead of L-methionine had no protective effects.
These results suggest that, although AVYS limits the supply of all amino acids to the embryo, embryopathy largely results from a deficiency of methionine. Furthermore, although endocytosis and degradation of proteins by the VYS supplies most amino acids to the embryo, free amino acids may be compensatory when this source is reduced. These results support those of previous investigations that suggest methionine is required for normal NT closure and that methionine is a limiting nutrient for embryonic development.
内脏卵黄囊异源抗血清（AVYS）具有致畸性，可在体内诱导一系列畸形，并在体外产生类似效应。大量研究支持这样的观点，即AVYS诱导的畸形是由胚胎营养缺乏导致的，而不影响母体营养状况。这为研究早期胚胎的营养需求以及各种营养素在先天性缺陷病因学中的作用提供了一个有用的模型。
在当前研究中，我们检测了蛋氨酸和其他营养素对AVYS体外诱导胚胎毒性的影响。在这些实验中，我们将大鼠胚胎（妊娠9.5天）与AVYS和/或不同浓度水平的蛋氨酸一起培养48小时。
在暴露于AVYS的培养物中添加L-蛋氨酸可减少畸形和开放性神经管；这种效应呈浓度依赖性。在L-蛋氨酸浓度相当于基础血清浓度50倍时，可完全防止AVYS诱导的畸形。使用D-蛋氨酸、L-亮氨酸或叶酸（5-甲基四氢叶酸，MTHF）替代L-蛋氨酸没有保护作用。
这些结果表明，尽管AVYS限制了胚胎对所有氨基酸的供应，但胚胎病主要是由蛋氨酸缺乏引起的。此外，尽管卵黄囊通过内吞作用和蛋白质降解为胚胎提供了大部分氨基酸，但当这种来源减少时，游离氨基酸可能具有补偿作用。这些结果支持了先前的研究结果，即正常神经管闭合需要蛋氨酸，且蛋氨酸是胚胎发育的限制性营养素。
