Reproductive Toxicity and Endocrine Disruption of Oral and Dermal Exposure to Pesticide Mixture in Male Rats

Abstract

The current study was performed to assess the risk and hazards of oral & dermal exposure to chlorpyrifos & cypermethrin mixture based on some reproductive & endocrine impaired parameters as well as histopathological alterations & histomorphometric study. Eighty-five Wister male rats (weighing 130-150g) were randomly classified into four groups (a, b, c and d). Each of group (a) and (b) were further subdivided into 5 subgroups used for determination of the oral and dermal LD50. While group (c) and (d) were classified into 3 subgroups which were used for oral and dermal treatments respectively. The first subgroups of (c) and (d) were considered as control. Rats of two subgroups (c) treated orally by 2 doses 4.26 mg/kg (1/20 LD50) and 2.84 mg/kg(1/30 LD50). Rats of two subgroups (d) treated by dermal application of 2 doses70.85mg/kg (1/30 LD50) and 42.51 mg/kg (1/50 LD50). The experiment was conducted for 65 consecutive days. The results revealed that, the tested pesticides mixture caused a significant reduction in reproductive organs weights, sperm count, sperm motility percent, alive sperm percent, pseudocholinesterase and serum testosterone levels in all treated groups especially the dermally treated groups (P≤0.05), moreover there was azoospermia in most of the group of rats treated with high dermal dose. The treated groups showed a significant increase in sperm abnormalities and composite score which represent sperm DNA fragmentation. Moderate to severe histopatholoical alterations were detected in testis and epididymis of treated rats in a dose and route dependant manner in the form of germ cell desquamation, multinucleated giant cells formation and leydig cell vacuolization with disturbance in spermatogenesis. Moreover the histomorphometric parameters analysis detected significant (P≤0.05) reduction of diameter, thickness, endothelium height & lumen of seminiferous tubules and also significant reduction of sertoli cell population. There was significant increase of blood vessel wall thickness.These results indicated that the tested formulation had synergistic effects and induced significant harmful effects on male reproductive system which were more pronounced with dermal exposure.