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The effect of nanoparticle-rich diesel exhaust (NR-DE) on the testicular function and factors related with the biosynthesis of testosterone gene expression were investigated in mice. Male C57BL/Jcl mice were exposed to clean air, low-dose NR-DE (Low NR-DE), high-dose NR-DE (High NR-DE) or filtered diesel exhaust (F-DE) for 8 weeks. We found that the mice exposed to High NR-DE had significantly higher testosterone levels than those in the control and F-DE groups. To determine the effects of NR-DE on testicular testosterone production, interstitial cells dissected from the male mice which were exposed to NR-DE, F-DE, or clean air for 8 weeks were incubated with or without human chorionic gonadotropin (hCG; 0.1 IU/mL) for 4 h. The concentrations of testosterone in the culture media were measured. The testosterone production was significantly increased in with or without hCG of High NR-DE exposed group, and significantly decreased in both with or without hCG of F-DE exposed groups. Moreover, several genes, which is associated with testicular cholesterol synthesis, HMG-CoA, LDL-R, SR-B1, PBR, and P450scc, P450 17α, and 17β-HSD were determined in the testis of adult male mice. The results showed High NR-DE exposure significantly increased the expression of these genes. Whereas, the levels in the F-DE exposure group returned to those in the control group, implicating that the nanoparticles in DE contribute to the observed reproductive toxicity. We conclude that enhancement of testosterone biosynthesis by NR-DE exposure may be regulated by increasing testicular enzymes of testosterone biosynthesis. [ABSTRACT FROM AUTHOR]

Background: Nanoparticle-rich diesel exhaust (NR-DE) has potentially adverse effects on testicular steroidogenesis. However, it is unclear whether NR-DE influences steroidogenic systems in the brain. Objective: To investigate the effect of NR-DE on hippocampal steroidogenesis of adult male rats in comparison with its effect on the testis. Methods: F344 male rats (8-week-old) were randomly divided into four groups ( n = 8 or 9 per group) and exposed to clean air with 4.6 ± 3.2 μg/m3 in mass concentration, NR-DE with 38 ± 3 μg/m3 (a level nearly equivalent to the environmental standard in Japan (low NR-DE)), NR-DE with 149 ± 8 μg/m3 (high NR-DE), or filtered diesel exhaust with 3.1 ± 1.9 μg/m3 (F-DE), for 5 hours/day, 5 days/week, for 1, 2 or 3 months. F-DE was prepared by removing only particulate matters from high NR-DE with an HEPA filter. Results: Exposures to the high NR-DE for 1 month, and low NR-DE for 2 months, significantly increased or tended to increase plasma and testicular testosterone levels compared to clean air exposure, which might have resulted from the increased expression of mRNA of steroidogenic acute regulatory protein and its protein in the testes of rats. In the hippocampus, high NR-DE exposure for 1 month significantly increased the androstendione level compared to the clean air exposure, while no significant difference was observed in the steroidogenesis between fresh air exposure and any exposure to NR-DE or F-DE. Conclusion: NR-DE may influence steroidogenic enzymes in the testis, but not those in the hippocampus. [ABSTRACT FROM AUTHOR]

Abstract: We previously reported that exposure to low (22.5±0.2nm in diameter, 15.4±1.0μg/m3 in mass weight, 2.27×105/cm3 in mean number concentration), and medium (26.1±0.5nm, 36.4±1.2μg/m3, 5.11×105/cm3) concentrations of nanoparticle-rich diesel exhaust (NR-DE) for 1 and 2 months (5h/day, 5 days/week) significantly increased plasma testosterone in male Fischer 344 rats, whereas exposure to a high concentration (27.1±0.5nm, 168.8±2.7μg/m3, 1.36×106/cm3) did not. The present study attempts to clarify the mechanism of this elevation. Low and medium exposures to NR-DE for 1 and 2 months significantly increased steroidogenic acute regulatory protein (StAR)- and cytochrome P450 side-chain cleavage (P450scc)-mRNA and their protein expressions in the testis of rats, in which the elevation pattern was very similar to that of plasma testosterone levels. Interestingly, both exposure levels for 1 month significantly increased growth hormone (GH) receptor expression in the testis, and low exposure also increased testicular insulin-like growth factor I-mRNA levels and hepatic microsomal cytochrome P450 2C11-mRNA and their protein levels in rats. These two factors are thought to be related to growth hormone secretion. Disruption of testosterone biosynthesis by NR-DE exposure may be a mode of action for reproductive toxicity, which may, in part, be regulated by increasing StAR and P450scc expressions via GH signalling. [Copyright &y& Elsevier]

Abstract: We investigated the effects of in utero exposure to nanoparticle-rich diesel exhaust (NR-DE) on reproductive function in male rats. Pregnant F344 rats were exposed to NR-DE (148.86μg/m3, 1.83×106 particles/cm3, 3.40ppm CO, 1.46ppm NOx), filtered diesel exhaust (F-DE; 3.10μg/m3, 2.66particles/cm3, 3.30ppm CO, 1.41ppm NOx), or clean air (as a control) from gestation days 1 to 19 (gestation day 0=day of sperm-positivity). Male offspring were examined on postnatal day 28. The relative weights of the seminal vesicle and prostate to body weight were decreased after exposure to NR-DE or F-DE compared with controls. Serum concentrations of testosterone, progesterone, corticosterone, and follicle stimulating hormone and testicular concentrations of steroidogenic acute regulatory protein and 17β-hydroxysteroid dehydrogenase mRNA were decreased after exposure to NR-DE or F-DE compared with control levels. In contrast, serum concentrations of immunoreative inhibin were increased after exposure to NR-DE or F-DE compared with control levels, whereas transcription of follicle stimulating hormone receptor mRNA was increased in the NR-DE exposure group only. These results suggest that prenatal exposure to NR-DE or F-DE leads to endocrine disruption after birth and suppresses testicular function in male rats. Because both the NR-DE and F-DE-exposed groups reacted to the same extent, the nanoparticles in DE did not contribute to the observed reproductive toxicity. [Copyright &y& Elsevier]