Flynn T J, Gibson R R, Johannessen J N
Food and Drug Administration, Center for Food Safety and Applied Nutrition/Division of Toxicological Studies, Laurel, Maryland 20708.
Teratology. 1993 Aug;48(2):161-8. doi: 10.1002/tera.1420480210.
Approximately 50% of untreated presomite rat embryos in culture have demonstrated inversions of cardiac looping (laeval instead of dextral) or tail flexure (left-sided instead of right-sided), or both. This spontaneous situs inversus (SI) was not accompanied by growth inhibition or any other observable defects. The incidence of SI was directly related to the stage at dissection, and all heart defects and most flexure defects were eliminated by delaying explantation to the early somite stage. The incidence of SI was not lowered significantly either by removal of endogenous catecholamines from the culture serum by dialysis or by inclusion of alpha- or beta-adrenergic antagonists in the medium. However, the alpha-adrenergic agonist L-phenylephrine (50 micrograms/ml) increased the incidence of SI to 73%. These findings appear to rule out adrenergic mechanisms as a cause of spontaneous SI in cultured, neural plate-staged rat embryos but suggest a mechanism, yet unknown, that is additive with SI induced by alpha-adrenergic agonists. The low incidence of non-SI-related defects suggests that the high incidence of SI is not an artifact of suboptimal culture conditions. The virtual absence of SI in embryos cultured in bovine serum, a medium in which overall embryonic growth and development were retarded, provides further evidence against nonspecific artifacts.
在培养过程中，约50%未经处理的原肠胚期大鼠胚胎出现了心脏环化反转（左旋而非右旋）或尾部弯曲（左侧而非右侧），或两者皆有。这种自发性内脏反位（SI）并未伴有生长抑制或任何其他可观察到的缺陷。SI的发生率与解剖时的阶段直接相关，通过将外植推迟到早期体节阶段，所有心脏缺陷和大多数弯曲缺陷都得以消除。通过透析去除培养血清中的内源性儿茶酚胺，或在培养基中加入α-或β-肾上腺素能拮抗剂，SI的发生率均未显著降低。然而，α-肾上腺素能激动剂L-去氧肾上腺素（50微克/毫升）使SI的发生率增加到73%。这些发现似乎排除了肾上腺素能机制是培养的神经板期大鼠胚胎自发性SI的原因，但提示了一种尚不清楚的机制，该机制与α-肾上腺素能激动剂诱导的SI具有累加作用。与SI无关的缺陷发生率较低，这表明SI的高发生率并非培养条件欠佳导致的假象。在牛血清中培养的胚胎几乎没有出现SI，在这种培养基中胚胎的整体生长和发育均受到抑制，这进一步证明了不存在非特异性假象。
