Evidence that spontaneous situs inversus in cultured neural plate staged rat embryos is additive with and not mediated through adrenergic mechanisms.
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.
Flynn
T J
TJ
Food and Drug Administration, Center for Food Safety and Applied Nutrition/Division of Toxicological Studies, Laurel, Maryland 20708.
Gibson
R R
RR
Johannessen
J N
JN
D000322:Adrenergic Agonists / Q000494:pharmacology; D000818:Animals; D016477:Artifacts; D002395:Catecholamines / Q000502:physiology; D046508:Culture Techniques; D005260:Female; D009420:Nervous System / Q000196:embryology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012857:Situs Inversus / Q000209:etiology*; D013566:Sympathomimetics / Q000494:pharmacology*
D000322:Adrenergic Agonists; D002395:Catecholamines; D013566:Sympathomimetics