OBJECTIVETo evaluate the reproduction toxicity of the mixture composed of dichlorvos, dimethoate and malathion synergistic effect on male mice, and further explore its possible mechanisms.

METHODSThe 105 male mice were divided into 7 groups, including control (0 mg/kg), mix low (10.8 mg/kg), mix medium (21.5 mg/kg), mix high dose (43.0 mg/kg), dichlorvos (5.1 mg/kg), dimethoate (12.6 mg/kg) and malathion (25.3 mg/kg) group. The oral gavage for successive 35 days, and the mice were sacrificed on the 36(th) day. The body weight, and the quantity, activity and morphology of sperms were examined. The levels of sexual hormone were measured, including testosterone (T), follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E(2)). Pathological changes of testicle and epididymis were observed by morphology, pathology and electron microscope.

RESULTSAfter 14 days exposure, the body weights of the mice were lower in the mix-high dose group ((22.40 ± 3.07) g) than those in control group ((26.73 ± 2.82) g) (P < 0.05). After 28 days exposure, the body weights of the mice were also lower in the mix-medium dose group ((30.00 ± 4.93) g) than those in control group ((33.13 ± 3.29) g) (P < 0.05). The sperm counts and sperm motility decreased significantly as the toxic concentration arised. Comparing to control group ((373.33 ± 14.65)×10(6)/g weight of epididymis and (75.17 ± 7.68)%), the spermatozoa count and sperm motility had decreased in mix-medium and mix-high dose groups ((321.17 ± 18.19)×10(6)/g weight of epididymis, (225.00 ± 19.67)×10(6)/g weight of epididymis, and (64.67 ± 9.91)%, (57.83 ± 9.66)%), and the sperm abnormality rates were higher in mix-medium and mix-high groups ((43.33 ± 8.66)‰ and (55.00 ± 13.80)‰) comparing to those in control group ((32.67 ± 8.17)‰). Compared to those in control group (FSH (1.41 ± 0.20), E(2)(17.32 ± 2.72), LH (8.75 ± 1.32) and T (3.45 ± 0.80) nmol/L), the serum level of FSH (3.14 ± 0.62) and (3.85 ± 0.37) nmol/L, E(2) (36.81 ± 6.68) and (43.76 ± 9.82) nmol/L in mix-medium and mix-high dose group increased (P < 0.01), while the level of LH (5.21 ± 1.23) and (4.27 ± 1.09) nmol/L and T (1.37 ± 0.38) and (0.73 ± 0.18) nmol/L decreased (P < 0.01). The morphological and ultramicrostructure results of testicle and epididymis indicated that the mature sperm numbers were decreased, and the cacoplastic sperm head and the tail of spermatozoon were observed in mix-high dose groups.

CONCLUSIONThe dichlorvos, dimethoate and malathion mixture had synergistic reproductive toxicity to the testicle and epididymis structure and function, and thus leading to the process of generation cell cytopoiesis abnormalities, simultaneously the hypothalamus-pituitary-gonad axis were also affected and thus resulted in parasecretion.