Effects of melatonin in rats in the initial third stage of pregnancy exposed to sub-lethal doses of herbicides.

Exposure to the herbicides Paraquat (PQ) and Roundup® may cause cell lesions due to an increase in oxidative stress levels in different biological systems, even in the reproductive system.

OBJECTIVE: Evaluate the possible changes in reproductive parameters and hepatic, as well as its prevention by simultaneous application of melatonin.

METHODS: Thirty-five female rats at the age of 3 months were divided into seven groups: three groups exposed to sub-lethal doses of the herbicides PQ (50mg/kg) and Roundup® (500mg/kg) (n=5, G2, G3 and G4); three groups exposed to herbicides and simultaneous treatment with 10mg/kg of Melatonin (n=5, G5, G6 and G7) and control group (n=5, G1) from the first to the seventh day of pregnancy. On the seventh day of pregnancy, the rats were anesthetized and euthanized, followed by laparotomy to remove their reproductive tissues and liver. Body and ovary weights were taken and the number of implantation sites, corpora lutea, preimplantation losses, implantation rates were counted and histopathology of the implantation sites, morphometry of the surface and glandular epithelia of endometrium and hepatic oxidative stress were undertaken.

RESULTS: The present study shows the decrease in body and ovary weight, decrease in the number of implantation sites, implantation rate, in the total number of corpora lutea and increase of preimplantation percentages were observed when compared to the G1: Fig. 1 and Table 1, (p>0.001 ANOVA/Tukey). The histopathological analysis of the implantation sites showed a disorder of the cytotrophoblast and cell degeneration within the blastocyst cavity in Fig. 4. Morphometry revealed a reduction in surface and glandular epithelia and in the diameter of the endometrial glands (Table 2; p>0.05 ANOVA/Tukey), whereas in liver, serum levels of thiobarbituric acid reactive substances (TBARS) were found to be significantly elevated (Fig. 2; p>0.001; p>0.05 ANOVA/Tukey), and serum level of reduced glutathione (GSH) was significantly lower (Fig. 3; p>0.001 ANOVA/Tukey). However, treatments with melatonin exhibited improvements in reproductive parameters, as well as reduced lesions in the implantation sites (Fig. 4.) and in serum levels TBARS (Fig. 2; p>0.001 ANOVA/Tukey), serum levels GSH (Fig. 3; p>0.001; p>0.05 ANOVA/Tukey).

CONCLUSIONS: These results reveal that melatonin is a protective agent against experimentally induced maternal/embryo toxicity with herbicides and favoring normalization of reproductive parameters and hepatic.