Lee H, Nagele R G, Pietrolungo J F
Teratology. 1982 Feb;25(1):19-25. doi: 10.1002/tera.1420250104.
The toxic and teratologic effects of caffeine on chick embryos explanted at stages 4-7 and cultured for 19-22 hours were investigated. Caffeine, at 200-300 micrograms/ml, significantly increased the incidence of neural tube defects regardless of the developmental stage at treatment. Concentrations of 500 micrograms/ml or higher inhibited morphogenesis of nearly all organ primordia. In general, the effects of caffeine were concentration dependent and younger embryos were more susceptible to treatment than their older counterparts. Microscopic studies confirmed that the developing neuroepithelium was most sensitive to treatment. Caffeine, at concentrations sufficient to inhibit neural tube closure, caused no apparent alteration in the ultrastructure of cellular components except that apical microfilament bundles were thinner and less conspicuous than usual. Furthermore, caffeine (400 micrograms/ml) selectively inhibited uplifting of neural folds (and hence, closure of the neural tube) in embryos explanted at stage 8 and cultured for 4-6 and 16 hours. Affected neuroepithelial cells lacked the typical bottle-shaped characteristic and folded apical surfaces. Overall results of this study suggest that caffeine causes neural tube defects, at least in part, through its inhibitory action on the contractile activity of apical microfilament bundles in developing neuroepithelial cells.
研究了咖啡因对4-7期取出并培养19-22小时的鸡胚的毒性和致畸作用。咖啡因浓度为200-300微克/毫升时，无论处理时的发育阶段如何，都会显著增加神经管缺陷的发生率。500微克/毫升或更高的浓度会抑制几乎所有器官原基的形态发生。一般来说，咖啡因的作用呈浓度依赖性，较年轻的胚胎比年长的胚胎对处理更敏感。显微镜研究证实，发育中的神经上皮对处理最敏感。咖啡因在足以抑制神经管闭合的浓度下，除了顶端微丝束比平时更细且不明显外，未引起细胞成分超微结构的明显改变。此外，咖啡因（400微克/毫升）选择性抑制8期取出并培养4-6小时和16小时的胚胎中神经褶的隆起（从而抑制神经管的闭合）。受影响的神经上皮细胞缺乏典型的瓶状特征和顶端表面折叠。本研究的总体结果表明，咖啡因至少部分通过其对发育中神经上皮细胞顶端微丝束收缩活性的抑制作用导致神经管缺陷。
