Experimental Study Of The Effect Of Short Phthalates Exposure On The Reproductive System Of Male Rats

Object:To evaluate the effect of DEHP exposure during neonatal period on the reproductive system of male rats.Methods:42 newborn rats were divided into three groups.The male offspring were gavaged daily according to design(contorl,250mg/kg,500mg/kg)from the first day on born to next 15 day(PND15).When PND36,each group randomly selected 6 SD rats and took testis by 10% chloral hydrate anesthesia.Then the effect on reproductive system of SD rats were observed at PND90.Then trying to explore the effect of Nrf2 and notch signaling pathway on DEHP-induced testicular injury.Methods: The neonatal SD rats were divided into three groups: control group(corn oil),DEHP 250mg/kg exposure group and DEHP 500mg/kg exposure group.From PND1 to PND15,Three group was avaged with corn oil,150mg/kg DEHP,500mg/kg respectively.At PND36,each group randomly selected 6 SD male rats and took its testis under 10% chloral hydrate anesthesia.At PND90,all testis were took from SD male rats after mating test.Then the epididymal tissue were used to sperm count and sperm abnormal rate detection.At PND1,PND10,PND20,PND36 and PND90,the AGD of each group of SD male mice was measured.Testicular tissue obtained at PND36 were used for HE staining and measurement of oxidative stres-related indicators and notch1,Nrf2 key protein expression.Results:The AGD length of 250 mg/kg DEHP exposure group was lower than that of normal control group,while there was no significant difference in the coefficient of testis and epididymis,sperm count,teratozoospermic rate,and mating test,however,the testicular histology showed a slight disorder of seminiferous epithelium.While500mg/kg DEHP exposure group,the length of AGD,testicular organ coefficient was lower than the normal control group.Although there was no significant difference between the results of the epididymal viscera coefficient,mating test and sperm,the count of sperm abnormality rate was significantly higher than that in normal group.The morphology of testicular tissue in 500 mg/kg DEHP exposure group was changed.In 500 mg/kg DEHP exposure group,the levels of ROS,MDA and SOD activity in testis tissue were significantly higher than those in the control group(P <0.05)and the expression of ROS in the testis tissue was significantly lower than that in the control group(P <0.05).In 250 mg/kg DEHP exposure group,SOD activity and MDA were higher than those in the control group,but there was no statistical significance.and the expression of Nrf2 and notch1 protein was lower than that of the control group,the difference was statistically significant.Conclusion:The short-term exposure to 500 mg/kg DEHP in SD male rats resulted in a decrease in sperm quality after adulthood,which was manifested in the sperm abnormality rate.The short-term exposure to 250 mg/kg DEHP had no significant effect on adult reproductive function,but there were still histological slight change.DEHP exposure can lead to an increase in testicular tissue oxidative stress and the level of MDA was high,so that Nrf2 expression decreased,may indirectly affect the notch signaling pathway,then,notch1 protein expression was decreased.