Expression of c-Jun N-terminal kinase in hypospadiac penis of fetal rats induced by maternal exposure to di(- 2-ethylhexyl)phthalate

Objective To investigate the expression of c-Jun N-terminal kinase(JNK)in the hypospadiac penis of fetal rats induced by maternal exposure to di(-2-ethylhexyl)phthalate(DEHP)in order to explore the etiology of hypospadias.Methods Pregnant rats of 12 gestation days(GD12) were randomly divided into test and control groups,20 for each.The rats in test group were treated with DEHP dissolved in 1.5 ml soybean oil by lavage at a dosage of 750 mg /(kg.d),while those in control group with 1.5 ml soybean oil,once a day from GD12 to GD19.Half of rats in each group were raised to postnatal day(PND) 30,and live male pups were counted and weighed,of which anogenital distance(AGD) were measured,and the hypospadias was observed.Fetal rats of the rest pregnant rats were obtained on GD20 by caesare an section,and determined for expression levels of JNK 1/2 mRNA and protein by real-time quantitative PCR(qPCR) and immunochemical assay respectively.Results On PND30,the number,body weight and AGD of live male pups in test group decreased significantly as compared with those in control group(each P 0.001),while the incidence rate of hypospadias was about 30.6%.However,compared with those in control group,the expression levels of JNK1 and JNK2 mRNAs in penis of fetal rats in test groups increased significantly(P 0.05),while the expression levels of JNK1 and JNK2 proteins showed increasing tendencies(P 0.05).Conclusion DEHP-induced congenital hypospadias might be associated with the abnormal expression of JNK signal pathway in hypospadiac penis of fetal rats.