Di-n-butyl phthalate (DBP) is an inexpensive and widely used plasticizer prevalent in daily life and industrial production, and it is also a common environmental pollutant. Classified as an anti-androgenic environmental endocrine disruptor, DBP shares a similar but not identical mechanism of action with flutamide. DBP exerts prominent testicular toxicity, embryonic toxicity, and reproductive teratogenicity in animals. It markedly reduces systemic testosterone levels and triggers pathological lesions in the male reproductive system, including testicular atrophy, cryptorchidism, epididymal dysplasia or agenesis, and hypospadias in the testes, epididymides, accessory sex glands and external genitalia. In addition to flutamide, diethylstilbestrol (DES) and DBP, benzoate and aspirin can also induce hypospadias malformation in mice. Given that patients with clinical hypospadias frequently present abnormal metabolism of sex hormones, particularly androgens, most hypospadias animal models are established by regulating host hormone levels through drug intervention. Hypospadias is not merely a local anatomical malformation, but also a localized manifestation of systemic endocrine disorders. Drug-induced hypospadias primarily results from disrupted apoptosis and proliferation of ventral urethral epithelial cells in fetal offspring during intrauterine development. Accordingly, the location of hypospadias lesions is closely correlated with the gestational age at drug exposure. The DBP-induced rat hypospadias model provides a reliable experimental basis for exploring the etiology of congenital pediatric hypospadias and clarifying the correlation between environmental pollution and the incidence of this congenital malformation.

SD rats (male and female, 3 months old)
Modeling method: Pregnant rats were intragastrically administered with DBP corn oil solution, and the hypospadias model was successfully established after 18 days.
Evaluation index: HE staining

Urethral HE staining