Studies of the etiology of thalidomide dysmorphogenesis

Abstract

Thalidomide was administered to pregnant rabbits in dosages of 150-250 mg/kg/day on days 8-12 of gestation. These females produced 40 offspring, 21 of which were deformed. Four control females produced 34 offspring, none of which was deformed. The C6 and C7 ganglia of day-13, -15, -17, and -21 control and experimental embryos and fetuses were examined electron microscopically. Degenerative changes were found in the neurons and axons of dorsal root ganglia in day-13 experimental embryos, i.e., at least 16h before the earliest signs of thalidomide dysmelia have been reported in rabbits (Vickers, '67). Since the dorsal root ganglia form in rabbits on days 11 and 12 the changes evident at day 13 indicate that degeneration of neurons and axons may be a pathogenetic factor in thalidomide-induced peripheral deformities.