The reproductive toxicity of the organophosphate pesticide 0, 0-dimethyl 0-4-nitrophenyl phosphorothioate (methyl parathion) in the male rat.

Methyl parathion (MP) is a pesticide widely used to protect crops but also illegally used in many countries for spraying homes and businesses to contain insects. The present study was planned to investigate the effects of MP on the male reproductive organs in the rat. Male Wistar rats (13-14 weeks old) were treated with MP and sacrificed as follows. Experiment 1:0 (water vehicle), 1.75, 3.5 or 7 mg/kg (i.p.) for 5 days and sacrificed on day 14; experiment 2:0, 0.5 or 1 mg/kg (i.p.) for 12 days and sacrificed on day 130; experiment 3: 0, 0.5 or 1 mg/kg (i.p.) for 12 days and sacrificed on day 77; experiment 4: 0, 0.75 or 1.5 mg/kg (i.p.) for 25 days and sacrificed on day 17; experiment 5: 0 or 3.5 mg/kg (p.o.) for 25 days and sacrificed on day 17 after the last exposure. The reproductive organs were removed, weighed and processed for histopathological analysis. Structural changes, for example the morphology of the epithelium and the lumina of the organs, were observed in all animals. Biochemical estimates of acid phosphatase (ACP), cholesterol, total protein, uric acid, and vitamin C were conducted in the epididymes. The weight of the epididymes increased in experiment 2 in a dose-dependent pattern (p < 0.01) and decreased in experiments 4 and 5 (p < 0.01). The weight of the ductus deferens decreased in experiment 3 at 1 mg/kg dose level (p < 0.001) and increased in experiment 5 (p < 0.05). The weight of the seminal vesicle decreased in experiment 3 at both 0.5 mg/kg and 1 mg/kg dose levels (p < 0.001), and increased in experiment 5 (p < 0.01). The weight of the prostate decreased in experiments 4 (in a dose-dependent pattern) and 5 (p < 0.001). ACP levels decreased in experiment 4 (p < 0.001) with a greater effect at 0.5 mg/kg than at 1 mg/kg. In experiment 5 (p < 0.01) cholesterol levels decreased to less than 50% of the control level for this experiment (p < 0.01) and protein levels also decreased (p < 0.01). Vitamin C levels decreased in a dose-dependent pattern in experiments 4 (p < 0.001) and 5 (p < 0.01). There were no effects on uric acid level. Sperm density was decreased in the epididymes of the rats treated and the epithelium of the epididymis and ductus deferens showed cellular necrosis, brush-border disruption and nuclear pyknosis. Nuclei were haloed, except in experiment 2 and the 0.5 mg/kg group of experiment 3. Methyl parathion did not induce significant changes in the structure of the seminal vesicle and prostate, except that epithelial folding was shorter than in the control. In conclusion, MP is a reproductive toxicant in the male rat and causes deterioration in the structural integrity of the reproductive organs and also the biochemical parameters in the epididymis.

Dermal exposure to the herbicide-paraquat results in genotoxic and cytotoxic damage to germ cells in the male rat.

The effects of exposure to low doses of paraquat, a herbicide, via the dermal route were studied on the spermatozoa of Sprague-Dawley rats. Paraquat (1, 1'-dimethyl-4, 4'-bipyridinium dichloride) was administered once a day for five days, at intervals of 24 h at 0, 6, 15 and 30 mg/kg, and the rats were sacrificed on days 7, 14, 28, and 42 after the last exposure. The sperm suspensions were obtained by mincing the caudae epididymes and ductus deferens for the purpose of performing a sperm morphology test, sperm count and analysis of sperm mortality and sperm motility, as per the standard procedures. The sperm count was decreased (p < 0.05) only on days 7 and 14 but sperm abnormalities increased on all days (p < 0.05). Sperm mortality increased at higher dose-levels (p < 0.05) except on day 42, and motility was affected by 30 mg/kg only on day 42. In conclusion, paraquat is a genotoxic and cytotoxic agent to germ cells in the male rat.

Induction of seminiferous tubular atrophy by single dose of 5-fluorouracil (5-FU) in Wistar rats.

Antimetabolite, 5-fluorouracil (5-FU) is known to cause testicular damage by epithelial sloughing and cell killing. However, it is not known whether 5-FU induces tubular atrophy and the fate of exfoliated germ cells. Present study was conducted to evaluate these effects of 5-FU on rat testis. Animals were injected, single dose of 5-FU (10.50 & 100 mg/kg, i.p.) and sampled at 1, 3, 15 and 30 day following the treatment. The testes were perfusion fixed by Bouin's fluid. Five micron thick paraffin sections of testes and epididymis were stained with haematoxylin and eosin. Slides were examined for the incidence of abnormal tubules (per 200 tubules), tubular diameter (STD), epithelial height (SEH) and for the presence of germ cells in the epididymis. Data were analysed by Mann-Whitney 'U' test. The testes weight, STD, SEH were decreased (P < 0.05-0.01) in treated animals. The abnormal tubules were increased in a dose dependent manner with atrophic tubules seen on 30 d. The exfoliated germ cells have not blocked the post testicular ductal system and found in the epididymis in a dose dependent manner. The present study concludes that 5-FU causes tubular shrinkage and atrophy. Further, epididymis is involved in the phagocytosis of germ cells.

5-fluorouracil (5-FU) induces the formation of giant cells and sloughing of seminiferous epithelium in the rat testis.

The chemotherapeutic agent, 5-fluorouracil (5-FU) has been widely used in the treatment of a variety of cancers. Its effect on the testis has not been substantially studied. Present study was conducted to evaluate the gonadotoxicity of 5-FU in male albino rats. Animals were injected with single dose of 5-FU (10, 50 and 100 mg/kg, i.p.) and sampled on 1, 3, 15 and 30 day post exposure. Animals were anaesthetised, testes were perfusion fixed by Bouin's fluid. Five micron thick paraffin sections were stained with haematoxylin and eosin. Slides were screened for the incidence of partially and extensively sloughed tubules. Data were analysed by Mann Whitney 'U' test. Only 100 mg/kg induced multinucleated cells on 3rd day. All doses of 5-FU induced sloughing of the seminiferous epithelium. Maximum number of partially sloughed tubules were seen on third day. Partial sloughing was not dose dependent except on 15th day. The extensive sloughing was dose dependent except on 30th day. The result indicates that all the doses of 5-FU tested in this study cause sloughing of epithelium and only 100 mg/kg induces the formation of giant cells on third day.