Fujinaga M, Lowe L A, Kuehn M R
Department of Anesthesia, Stanford University School of Medicine, Stanford, California 94305, USA.
Teratology. 2000 Nov;62(5):317-24. doi: 10.1002/1096-9926(200011)62:5<317::AID-TERA5>3.0.CO;2-L.
Normal development of the left/right (L/R) body axis leads to the characteristic sidedness of asymmetric body structures, e.g., the left-sided heart. Several genes are now known to be expressed with L/R asymmetry during embryogenesis, including nodal, a member of the transforming growth factor-beta (TGF-beta) family. Mutations or experimental treatments that affect L/R development, such as those that cause situs inversus (reversal of the sidedness of asymmetric body structures), have been shown to alter or abolish nodal's asymmetric expression.
In the present study, we examined the effects on nodal expression of alpha(1)-adrenergic stimulation, known to cause a 50% incidence of situs inversus in rat embryos grown in culture, using reverse transcription-polymerase chain reaction assay and whole-mount in situ hybridization assay.
In embryos cultured with phenylephrine, an alpha(1)-adrenergic agonist, nodal's normal asymmetric expression only in the left lateral plate mesoderm was altered. In some treated embryos, nodal expression was detected in either the left or right lateral plate mesoderm. However, most treated embryos lacked lateral plate mesoderm expression. In addition, the embryos that did show expression were at a later stage than when nodal expression is normally found.
Our results demonstrate that alpha(1)-adrenergic stimulation delays the onset and perturbs the normal asymmetric pattern of nodal expression. Either of these effects might contribute to situs inversus.
左右体轴的正常发育导致不对称身体结构的特征性定位，例如心脏位于左侧。现已发现，包括转化生长因子-β（TGF-β）家族成员Nodal在内的几个基因在胚胎发生过程中呈现左右不对称表达。影响左右发育的突变或实验处理，如导致内脏反位（不对称身体结构定位反转）的那些处理，已被证明会改变或消除Nodal的不对称表达。
在本研究中，我们使用逆转录-聚合酶链反应分析和全胚胎原位杂交分析，研究了已知在培养的大鼠胚胎中会导致50%内脏反位发生率的α1-肾上腺素能刺激对Nodal表达的影响。
在用α1-肾上腺素能激动剂去氧肾上腺素培养的胚胎中，Nodal仅在左侧侧板中胚层的正常不对称表达发生了改变。在一些处理过的胚胎中，在左侧或右侧侧板中胚层均检测到了Nodal表达。然而，大多数处理过的胚胎缺乏侧板中胚层表达。此外，确实显示有表达的胚胎处于比正常发现Nodal表达时更晚的阶段。
我们的结果表明，α1-肾上腺素能刺激会延迟Nodal表达的起始并扰乱其正常的不对称模式。这些影响中的任何一种都可能导致内脏反位。
