Excessive stimulation of serotonin2(5-HT2) receptors during late development of chicken embryos causes decreased embryonic motility, interferes with hatching, and induces herniated umbilici

The existence and functional significance of 5-HT2 receptors in chicken embryos was studied by injecting the selective agonist dimethoxyiodophenylaminopropane (DOI), alone or in conjunction with the selective 5-HT2 antagonist ritanserin (RIT), into domestic chicken eggs with embryos of varying ages. DOI caused dose-dependent reductions in hatchability and herniated umbilici in hatchlings. These effects were observed after injection early, mid, or late during embryonic development, with evidence of the toxic effects of DOI being greater in older embryos, probably due to 5-HT2 receptor activation late in development, even after injecting DOI as early as on day 3 of embryogenesis. This is based upon the fact that embryos in eggs injected with DOI early continued to develop apparently normally, failing to hatch, often after pipping their shells. Additionally, those that hatched often did so with herniated umbilici, as did late-exposed embryos, indicating that DOI's effects upon this organ were most likely mediated during the prehatching period (i.e., days 18-20). The agonist's selectivity was confirmed by the capacity of RIT to dose dependently block both of these toxic effects of DOI. Reduced embryonic motility monitored on day 19, after injection of DOI on the evening of day 18, suggests that excessive activation of 5-HT2 receptors late during development of this species interferes with some normal embryonic behaviors and physiological changes necessary for inducing and/or maintaining the hatching process.