The role of androgen-induced growth factor (FGF8) on genital tubercle development in a hypospadiac male rat model of prenatal exposure to di-n-butyl phthalate.

Fibroblast growth factor 8 (FGF8) is an androgen-induced growth factor (AIGF) that is crucial for embryonic development. This study was developed to investigate the role of FGF8 in developmental abnormalities of the genital tubercle (GT) in hypospadiac male rats when prenatally exposed to di-n-butyl phthalate (DBP). DBP was administered to timed-pregnant rats to establish the hypospadiac rat model where the incidence of hypospadias in male offspring was 43.6%. On postnatal day (PND) 7, decreased mRNA and protein expression levels for androgen receptor (AR) and FGF8 were observed in the GT of hypospadiac rats. Decreased serum testosterone (T) levels were observed in groups displaying hypospadias, which was confirmed using histological analysis. Further anatomical examination using digital photography helped to reveal visualized expression of dysplasia in organs strongly associated with hypospadias. In addition, changes in body weight (BW) and anogenital distance (AGD) were recorded, showing definitive decreases. Collectively, these data clearly demonstrate an interaction between androgen and FGF8, which might play an important role in the occurrence of hypospadias and abnormal organ development induced by DBP.