Objective      To investigate the expression of extracellular signal-regulated kinase 1/2 (ERK1/2) 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      Forty timed-pregnant rats were randomly divided into 2 groups

control

and DEHP induction group. The rats of the former group were given soybean oil

while those of later group were given gastric intubation of 750 mg/kg DEHP dissolved in soybean oil from gestation day (GD) 12 to 19. In each group

half of them (10 rats) were raised to deliver naturally

and live male pups were counted. The male pups’ weight and their anogenital distance (AGD) were measured on postnatal day (PND) 1

3

7

14

21 and 30

and the hypospadias was observed on PND 30. The left (10 rats) were caesarean delivered at GD 20

and fetal rats penis were collected for real-time quantitative polymerase chain reaction (qPCR) and immunochemical assay to determine the mRNA expression and protein phosphorylation level of ERK1/2.       Results      The hypospadias incidence of DEHP group was 28.2%. Compared with normal control group

the decreased numbers of live male pups

body weight and AGD on PND  1

3

7

14

21 and 30 were observed. The mRNA expression of ERK1 and ERK2 in the fetal rat penis of DEHP group was increased significantly (

P

0.05). And the protein phosphorylation levels of ERK1/2 in DEHP group also showed an increa-sing trend.       Conclusion      DEHP-induced hypospadias might be due to the over-expression of ERK1/2 in the fetal rat penis.