Role of epididymal inflammation in the induction of dominant lethal mutations in Fischer 344 rat sperm by methyl chloride.

Abstract

This study assessed the possible relationship between methyl chloride (MeCl)-induced epididymal inflammation and the formation of dominant lethal mutations in sperm of Fischer 344 rats. Groups of 40 males were exposed to MeCl (3000 ppm 6 hr/day for 5 days), with or without concurrent treatment with the anti-inflammatory agent 3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline (BW 755C; 10 mg/kg, i.p. 1 hr pre-and postexposure); BW 755C was shown previously to inhibit MeCl-induced epididymal inflammation. Control groups (n = 20) were either untreated, injected as described above with BW 755C, or injected on the afternoon of day 5 with triethylenemelamine (0.2 mg/kg), a known dominant lethal mutagen. Each male was caged with one female weekly for 3 weeks; 12-18 days after mating, females were killed to assess dominant lethal parameters. In females bred to MeCl-exposed males, significant increases were observed in postimplantation loss at postexposure week 1 (0.84 dead implants per female vs. 0.29 in untreated controls) and in dead implants/total implants at both week 1 (0.10 vs. 0.04 control) and week 2 (0.24 vs. 0.06 control). These increases were not observed in females bred to males treated with BW 755C during MeCl exposure. Coadministration of BW 755C to males along with MeCl also reduced the percentage of mated females with two or more postimplantation losses from 31% to 8% (week 1) and 30% to 12% (week 2). Therefore, the dominant lethal mutations induced by MeCl appear to be a consequence of its induction of inflammation in the epididymis. These data demonstrate the potential genotoxicity of inflammatory processes in vivo.

Pathogenesis of Male Reproductive Toxicity

“…If testosterone levels are inadequate, these particular cells will show progressive degeneration and depletion during the rst week of testosterone withdrawal. At later tim es, the process of maturation depletion results in generalized depletion of all elongating and m aturation phase spermatids (steps [11][12][13][14][15][16][17][18][19] [for review, see (50)] (Figure 6C). This and the degenerating pachytene sperm atocytes and round spermatids in stages VII and VIII provide a unique and sensitive m arker to recognize hormonally induced damage.…”

Histopathology of the Male Reproductive System II: Interpretation

“…This is a chronic, progressive lesion and in the coiled epididymal duct has the added complication of causing obstruction to the passage of sperm. Furthermore, the oxidative free radicals produced by inflammatory cells in contact with sperm can lead to genotoxic damage, which may have implications for male-mediated congenital defects and post-implantation losses (Chellman et al, 1986). The efferent ducts, which join the caput epididymis with the rete testis, are a particular site for damage.…”

Tribulus terrestris improves metronidazole-induced impaired fertility in the male mice

“…Our earlier findings reporting the reappearance of several spermatozoa in the epididymal lumen, as evidenced through histopathological study, following co-administrations of 500mg/kg BW/day of MTZ and 200mg/kg BW/day of the fruit extract of TT 36 , also support the present study. Therefore, improvements in the number of live implants and pre- and post-implantation losses might be due to the beneficial properties exhibited by the fruit extract of TT on the quality and quantity of spermatozoa, 43 – 47 thus increasing the fertility potential of the MTZ-treated mice.…”