Calcium homeostasis and early embryotoxicity in marine invertebrates

Chemicals of various origins: chlorambucil, maitotoxin, sigmoidines, caulerpenyne, tributyltin, thapsigargin, 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and retinoid CD 367 were assayed on the cleavage of sea urchin eggs, their embryonic development and mechanisms regulating Ca2+. homeostasis. Compounds were used at therapeutic doses or at concentrations which were previously shown to be cytotoxic. These molecules did not affect the fertilization of Paracentrorus lividus eggs but all of them delayed the first cleavage. Only chlorambucil and CD 367 retarded hatching. All compounds provoked embryonic abnormalities if development was followed up to the pluteus stage, 72 hr after fertilization. Chemicals inhibited the ability of ATP-driven Ca2+ accumulation by the eggs in non-mitochondrial intracellular stores. Chlorambucil, maitotoxin and sigmoidines provoked a release of the Ca2+ sequestered with kinetics comparable to those provoked by the Ca2+ ionophore A23187. Ca2+ permeability of the plasma membrane was greatly increased by maitotoxin and 2,4,5-T whereas the other compounds were without effect. A drug-induced change in the Ca2+ storage capacity of sea urchin eggs resulting in retardation of cleaving stages and in further developmental defects is discussed in view to the possibility of relating changes in Ca2+-homeostasis with teratogenicity.