Relationship between insecticide-induced short and wry neck and cervical defects visible histologically shortly after treatment of chick embryos.

In order to clarify the anatomical precursor of short and wry neck, 48-hr chick embryos were injected with 6.25-200 micrograms of the organophosphate (OP) insecticide diazinon and recovered either at 96 hr for histological evaluation or at 19 days for gross observation. Among embryos recovered at 96 hr, all receiving a dose of 25-200 micrograms showed, in serial cross sections, the cervical notochord severely folded in the vertical, horizontal, and diagonal planes and the adjacent neural tube variously folded (often with branching of its canal), deformed by the notochord, rotated, and/or displaced from the midline. Virtually all embryos injected with 6.25 or 12.5 micrograms were fully free of such abnormalities. The coinjection of 2-pyridinealdoxime methochloride (2-PAM, which protects the embryo from certain OP insecticide-induced teratisms) along with 200 micrograms of diazinon markedly reduced the notochord and neural wry neck at 19 days paralleled the 96-hr cervical histology: pronounced in all embryos receiving greater than or equal to 25 micrograms, virtually nonexistent in those receiving 6.25 or 12.5 micrograms. Though more marked at higher doses, wry neck occurred to varying extents at all doses, 6.25-100 micrograms. We conclude that 1) the primary insecticide effect is upon the notochord rather than the neural tube, 2) short neck is a direct consequence of notochord folding, 3) wry neck is apparently not linked with notochord folding, and 4) vertebral fusion is not the consequence solely of muscle paralysis as argued elsewhere. We propose that the notochord folds because diazinon disrupts normal formation of its sheath.