Dose-related effect by maternal exposure to di-(2-ethylhexyl) phthalate plasticizer on inducing hypospadiac male rats

The aim of this study was to evaluate dose-related effects on external genitalia of adult male offspring rats by maternal exposure to di-(2-ethylhexyl) phthalate (DEHP) plasticizer. Timed-pregnant rats were given DEHP by gastric intubation at doses of 0, 500, 750 or 1000 mg/kg body weight/day from gestation day 12–19 to establish a hypospadiac rat model. The hypospadias was observed and the incidence in three DEHP dosage levels was 10.7%, 30.6% and 37.0%, respectively. With exposed dose increased, mild, moderate and severe hypospadiac rats were distinguished and an increased incidence of severe hypospadias was observed. The other reproductive lesions like reduced penile length and anogenital distance/body weight were observed. The results indicated the dose-related external genitalia teratogenic toxicity, and graded hypospadias on male offspring was resulted from high dosage DEHP maternal exposure.

► For the first time, we found a suitable dosage of DEHP for the establishment of a hypospadiac rat model.
► We firstly observed dose-related and phenotype-related hypospadiac rats induced by maternal exposure to DEHP. The hypospadiac rats following DEHP-exposed were categorized as mild, moderate and severe three kinds of hypospadias.
► We firstly identified a direct relationship between DEHP highly exposed and short penis.