A Time-Course Characterization of Male Reproductive Toxicity in Rats Treated With Methyl Methanesulphonate (Mms)

Abstract

-Methyl methanesulphonate (MMS), a potent alkylating agent and testicular toxicant, was orally administered to rats for 5 days at doses of 20, 30, and 40 mg/kg. During the recovery period of 5 weeks, males were evaluated for multiple endpoints such as organ weights, fertility, and sperm parameters. The 5-week recovery periods are designated as follows: Day 1 (1 day after final treatment); Week 1, Week 2, Week 3, Week 4, and Week 5 (first, second, third, fourth, and fifth week after final treatment). A clear time-course of dominant lethals was observed. The peak severities of the dominant lethals were observed in Week 2. It was judged that the most sensitive cellular targets for the dominant lethals are late spermatids. Sperm examination revealed a clear time-course and dose-dependent changes in the frequency of sperm morphological abnormalities. The peak severities of the sperm morphological alterations in cauda epididymis were observed in Week 4. Sensitive cellular stages for the induction of sperm morphological abnormalities were judged to be late spermatocytes and early spermatids. The most frequently observed type of morphologically abnormal spermatozoa was tailless sperm, followed by no-hook head sperm. Although the initial cause for both sperm morphological alterations and dominant lethals was suggested to be genetic insult to the germ cells, there were no obvious relationships observed between these two findings.

In vitro responses to known in vivo genotoxic agents in mouse germ cells

“…So, we suggest that the rat is also a very important model for the investigation of the mechanisms and susceptibility of germ cells to genotoxicity. After MMS treatment, the sensitive cellular stage for induction of sperm morphological abnormalities was judged to be late spermatids [Kuriyama et al, ]. These results also indicated that all three compounds induced DNA damage in isolated germ cells in mouse as well as shown earlier in rat so strengthening the rodent data base.…”

Genotoxic effect and rat hepatocyte death occurred after oxidative stress induction and antioxidant gene downregulation caused by long term fluoride exposure

“…For the micronuclei test a positive control group (Pc n ¼ 5) received water and one dose of methyl methanesulfonate (MMS -Sigma, St. Louis, MA, USA) at a concentration of 20 mg/kg 24 h before euthanasia [17].…”

“…Thereafter, 3 mL biuret reagent received 50 mL of the sample. After 10 min, the samples were read at 540 nm, and the mean was used to calculate protein concentration in the sample with the following equation: absorbance e 0.0026/0.0073 17 . The pellet containing the mitochondrial fraction (0.5 mg protein), added to 3 mL medium containing 125 sucrose and 1 mM HEPES, pH 7.2e7.3, furnished absorbance kinetically monitored at 540 nm over a period of 15 min.…”

Toxicological evaluation of ametryn effects in Wistar rats

“…The animals were weighed, and received by gavage, an aqueous solution of ametryn (T1 and T2) or water only (Co) for a chronic period of 56 days. For the micronucleus test, a positive control group (PG) (n = 6) received by gavage water and, one day before the euthanasia, a single dose (20 mg/kg) of methyl methane sulfonate (MMS) (Kuriyama et al, 2005).…”