A Quantitative Ultrastructural Study of Motor and Sensory Lumbosacral Nerve Roots in the Thalidomide-Treated Rabbit Fetus

Abstract

A quantitative electron microscopic study was conducted on the dorsal and ventral nerve roots (L7-S1) supplying the hindlimbs of control and thalidomide-treated rabbit fetuses. The ventral roots at segmental levels L7 and S1 of treated nondeformed fetuses (TND) and deformed fetuses, demonstrated significant reductions (20-30%) of four of the parameters measured; total fascicular area (TFA), myelinated axon number (AN), Schwann cell counts (SCC) and axoplasmic area. In the dorsal roots of treated animals, thalidomide affected primarily segmental level S2, where significant reductions (15-30%) were observed in three parameters (TFA, AN, SCC). The occurrence of significant reductions in these measures in TND fetuses may indicate a neurotoxic action for thalidomide in the embryo. Despite apparent reductions in Schwann cell numbers in dorsal and ventral nerve roots, analyses of axon caliber and myelin sheath thickness indicated no evidence for any effects of thalidomide on the myelination of either sensory or motor axons. The segmental distribution of the axonal lesion, being maximal at segmental levels L7 and S1 in the ventral roots and at segmental level S2 in the dorsal roots, indicates a discrete period during development when nervous tissue is susceptible to the effects of thalidomide. The results of this study suggest thalidomide may have effects on neural development as well as on limb development.