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

Teratology. 2000 Nov;62(5):317-24. doi: 10.1002/1096-9926(200011)62:5<317::AID-TERA5>3.0.CO;2-L.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cloning, Molecular
  • DNA Primers / chemistry
  • Embryo, Mammalian / drug effects*
  • Embryo, Mammalian / metabolism
  • Female
  • In Situ Hybridization
  • Molecular Sequence Data
  • Nodal Protein
  • Organ Culture Techniques
  • Phenylephrine / pharmacology*
  • Polymerase Chain Reaction
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, alpha-1 / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Situs Inversus / etiology
  • Situs Inversus / genetics*
  • Situs Inversus / metabolism
  • Situs Inversus / pathology
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / genetics*

Substances

  • Adrenergic alpha-Agonists
  • DNA Primers
  • Nodal Protein
  • Receptors, Adrenergic, alpha-1
  • Transforming Growth Factor beta
  • Phenylephrine