Atrazine And Its Main Metabolite DACT Induce The Endocrine Disruption And Oxidative Damage In Male Mice

Atrazine(ATZ)is a widely used herbicide that makes it the most frequently detectecd herbicide in surface and ground waters.A number of researches demonstrate that ATZ is an endocrine disruptor of different organisms,also it can create oxidative stress in organisms.diaminochlorotriazine(DACT)is the major in vivo metabolite of ATZ detected in mice and rat plasma,urine and tissues.The aims of present experiments are to evaluate the endocrine disruption and oxidative stress induced by ATZ and its metabolite DACT.Firstly,peripubertal male ICR mice were orally administrated ATZ for 3 weeks at doses of 50,100 and 200 mg/kg/day.The body and liver weights decreased significantly,while the relative testis weights increased.Besides,all doses of ATZ significantly decreased the serum testosterone(T)concentration,but the serum estradiol(E2)concentration and aromatase activity were significantly increased in mice exposed to 100 and 200 mg/kg ATZ.All the results suggested that ATZ exposures hormone homeostasis in peripubertal male mice.Research also showed that exposed to 100 and 200 mg/kg ATZ for 3 weeks significantly reduced the transcript levels of the relative steroidogenic genes P450scc,P450 17a and 17?-HSD were in the testes of peripubertal mice.Secondly,adult male ICR mice were intraperitoneal injected by ATZ and DACT(0,100 and 200 mg/kg/bodyweight,respectively)every other day for a week,with conducting totally 4 times injection(day 1,day 3,day 5 and day 7)according to the body weights.The body,liver and testis weights significantly decreased especially in the 200 mg/kg ATZ and DACT treated groups.The hepatic activities of antioxidant enzymes including SOD increased significantly after 1 week treatment of 200 mg/kg ATZ,100 and 200 mg/kg DACT.Hepatic activities of CAT decreased and GST increased significantly by treatment with 200 mg/kg DACT.In serum,the GPX and GST activities and GSH content decreased significantly in 200 mg/kg DACT treated group.The one-week treatment of ATZ and DACT decreased the transcription levels of key genes of cholesterol transport and T synthesis including SR-B1,StAR,P450scc and P450 1 7a in the testes.In 200 mg/kg DACT treatment group,the serum T levels decreased significantly in mice.While both in 200 mg/kg ATZ and DACT treated groups testicular T levels decreased significantly.The results indicated that acute exposure to ATZ and its metabolite DACT can induce oxidative stress and endocrine disruption in male mice.And at the same doses,DACT exhibited much more toxic than ATZ.Finally,leydig cells(TM3)were treated with ATZ and DACT(0,100 and 200?M)for 24 h.In 200 ?M ATZ and DACT treatment groups,the GSH content also increased significantly in TM3 cells.Both doses of ATZ increased significantly the expression of Gst mNRA level in TM3 cells,while both doses of DACT increased the expression of Gpx mNRA level.The mRNA levels of Sod2 and Cat decreased significantly in 200 ?M ATZ treatment group,and only 200?M DACT decreased the mRNA levels of Cat in DACT groups.Moreover,200 ?M ATZ and DACT significantly decreased the mRNA expression of P45017? and 17?-HSD,while only 200?M ATZ decreased the mRNA expression of P450scc and CYP19?.In conclution,ATZ and DACT induced oxidative stress and endocrine disruption in male mice.These results are helpful to study the mammalian toxicological mechanism of ATZ and its main metabolite DACT.