alpha(1)-Adrenergic stimulation perturbs the left-right asymmetric expression pattern of nodal during rat embryogenesis

Background: Normal development of the left/right (L/R) body axis leads to t he characteristic sidedness of asymmetric body structures, e.g., the left-s ided 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 af fect L/R development, such as those that cause situs inversus (reversal of the sidedness of asymmetric body structures), have been shown to alter or a bolish nodal's asymmetric expression. Methods: In the present study, we examined the effects on nodal expression of alpha (1)-adrenergic stimulation, known to cause a 50% incidence of situ s inversus in rat embryos grown in culture, using reverse transcription-pol ymerase chain reaction assay and whole-mount in situ hybridization assay. Results: In embryos cultured with phenylephrine, an alpha (1)-adrenergic ag onist, nodal's normal asymmetric expression only in the left lateral plate mesoderm was altered. In some treated embryos, nodal expression was detecte d 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. Conclusions: Our results demonstrate that alpha (1)-adrenergic stimulation delays the onset and perturbs the normal asymmetric pattern of nodal expres sion. Either of these effects might contribute to situs inversus. (C) 2000 Wiley-Liss, Inc.