Developmental toxicity of toluene in male rats: effects on semen quality, testis morphology, and apoptotic neurodegeneration

In one study, pregnant Wistar rats were exposed to 1200 ppm toluene by inha lation 6 h a day from gestational day (GD) 7 to postnatal day (PND) 18. Spe rm analysis was performed in the adult male offspring at PND 110 bp using c omputer-assisted sperm analysis. Toluene if id not affect the semen quality of exposed rats. In another study, pregnant rats were exposed to 1800 ppm from GD 7 to GD 20, and the male offspring were killed at PND 11, 21 or 90. Paired testes weight, histopathology and immunoexpression of vimentin in S ertoli cells were used as markers of testis toxicity. In the brain, the num ber of apoptotic cells in the hippocampus and cerebellum were counted after visualisation by means of the TUNEL assay. Mean body weight in pups of exp osed darns was lower than in pops from control litters. This decrease was s till statistically significant at PND 11, but at PND 21 and 90 the body wei ght of toluene-exposed males tended to approach that of the controls. Absol ute and relative testes weights were reduced in all three age groups, altho ugh not to a statistically significant degree. Histopathological examinatio ns of the testis and immune-expression of vimentin did not reveal any diffe rences between toluene-exposed animals and control animals. In the hippocam pus! almost no apoptosis was observed in any age group, and there were no d ifferences in apoptotic neurodegeneration between male rats exposed to 1800 ppm and control animals at PND 11, 21 or 90. Generally. a marked increase in number of apoptotic cells was observed in cerebellar granule cells at PN D, 21 compared with the other age groups. Toluene induced a statistically s ignificant increase in the number of apoptotic cells in the cerebellar gran ule layer at PND 21. The mean was increased from 37 in the control group to 71 in the toluene-exposed group. Thus, the granular cell layer in cerebell um is a highly relevant tissue with which to study toluene-induced apoptosi s, because of the continuous migration of neurons and high frequency of neu ronal apoptosis during the weaning period. In summary, it is concluded, tha t neither pre- and postnatal exposure to 1200 ppm toluene nor prenatal expo sure to 1800 ppm induced significant effects on the reproductive parameters investigated. However, prenatal exposure to 1800 ppm toluene did increase neuronal apoptosis in the cerebellum of weaned male rats, possibly by delay ing postnatal migration of granule cells to their final destination, or by toluene-induced retardation of generalised fetal growth.