Investigation of androgenic and anti-androgenic effects of endosulfan, cypermethrin, 2,4-D and trifluralin by hershberger method in rats

The potential harmful effects of endocrine-disrupting chemicals (EDC) on human health, animals and environment constitutes a major concern as an important public health problem. The present study was aimed to investigate the androgenic and anti-androgenic effects of organochlorid (Endosulfan) and pyrethroid (Cypermethrin) pesticides and herbicides (2,4-D and Trifluralin), which have potential to accumulate in nature and widely used in Turkey, on serum LH and FSH levels and androgen-sensitive tissues (prostate, bulbourethral glands, vesicula seminalis, m.Levator ani) in peri-pubertal rat model with Hershberger assay. A total of 56 peri-pubertal 42 days old Sprague Dawley rats were used in the study. The first group was separated as sham castration. The remaining 49 rats were totally (testes and epididymis) castrated under xylazin+ketamine aneasthesia. After 10 days recovery period, rats were weighed and divided into further seven groups: Castration group; Testosterone Propionate (TP) group (0.5 mg/kg/day s.c. TP); TP+Flutamide group (25 mg/kg/day, oral gavage); TP+Endosulfan group (10 mg/kg/day, oral gavage); TP+2,4-D group (10 mg/kg/day, oral gavage); TP+Cypermethrin group (20 mg/kg/day, oral gavage); TP+Trifluralin group (15 mg/kg/gün, oral gavage). After 10 days application all animals weighed again. 24 hours after the last application, rats were decapitated and blood samples were obtained. Prostate, bulbourethral (Cowper) gland, vesicula seminalis and musculus levator ani (mLA) as well as liver and kidneys were dissected immediately and weighed. Serum testosterone, LH and FSH levels were determined with ELISA. Castration caused significant reduction in all androgen-sensitive tissue weights (p<0.001); whereas TP application to the castrated animals recovered this tissue weights to the levels of sham group (p<0.001). While Endosulfan, Cypermethrin and Trifluralin caused significant decrease in bulbourethral gland weights (p<0.01); 2,4-D significantly increased vesicula seminalis weights compared to TP group (p<0.01). None of the applied test compounds caused significant differences in prostate and m. Levator ani weights compared to TP group (p>0.05). 2,4-D, Cypermethrin and Trifluralin significantly increased serum FSH levels; but the increase in serum LH levels was only significant in Trifluralin group. In conclusion; data obtained from this study showed that 2,4-D has androgenic effects on vesicula seminalis whereas Endosulfan, Cypermethrin and Trifluralin have anti-androgenic effects on bulbourethral gland. It can be suggested that, these environmental pollutants could affect male reproductive functions negatively. Key Words: Endocrine disrupting chemicals (EDC), Endosulfan, Cypermethrin, 2,4-D, Trifluralin, Hershberger assay