Pathogenesis of Experimental Lumbosacral Agenesis in Rats

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  • Pathogenesis of Experimental Lumbosacra

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ABSTRACT Pathogenesis of lumbosacral agenesis following trypan blue treatment was studied in rats. Pregnant rats (on day 8 of pregnancy) were intraperitoneally injected with 2% trypan blue (40 mg/kg), and the fetuses at various stages of gestation were submitted to morphological examination. Every fetuses were observed under a stereoscop- ic microscope, and serial sections of the lumbosacral region were made for light microsco- py. Fetal growth was classified into 6 stages based on the fetal posture and the development of neutral tube. At Stage 2 (corresponding to gestational age of 237 2 6 hours) and at later stages, a cystic change was found stereoscopically on the dorsal side of the tail end in 23-33% of the fetuses. The cyst was unilocular or multilocular and was seen on one side or both sides of neural groove. After Stage 3 (240 +- 6 hours), the cysts were enlarged. At Stage 5 (252 +- 6 hours), cysts were various in shape and size. The initial histological lesion induced by trypan blue was edematous splitting of the intercellular spaces in the mesoderm and resultant cyst formation. After Stage 3, cysts in the mesoderm pushed the neural epithelium towards the back and caused deformation of the neural groove. After day 13, characteristic changes of lumbosacral agenesis, such as tail defect, short tail, and hind leg deformation, were observed in 20-30070 of the fetuses. At day 21, lumbosacral agenesis was recognized on soft X-ray films. The site and incidence of lumbosacral agenesis corresponded with those of cyst formation in an early gestation period. The present experiment showed that the cystic change in the mesoderm is the early and primary histological lesion of trypan blue-induced lumbosacral agenesis, and that alteration of the neural tube is secondary to the cystic change of the mesoderm.

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