Department of Urology, Shanghai First People's Hospital affiliated to Shanghai Jiaotong University, 85 Wujin road, Shanghai 200080, China.
Department of Urology, Wujiang City No.1 People Hospital affiliated to Nantong University, 169 Gongyuan road, Songling, Wujiang 215200, Jiangsu, China.
Toxicology. 2012 Mar 11;293(1-3):53-58. doi: 10.1016/j.tox.2011.12.010. Epub 2012 Jan 17.
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.
成纤维细胞生长因子 8（FGF8）是雄激素诱导的生长因子（AIGF），对于胚胎发育至关重要。本研究旨在探讨雄激素诱导的成纤维细胞生长因子 8（FGF8）在产前暴露于邻苯二甲酸二丁酯（DBP）的尿道下裂雄性大鼠生殖结节（GT）发育异常中的作用。DBP 被给予定时怀孕的大鼠以建立尿道下裂大鼠模型，其中雄性后代尿道下裂的发生率为 43.6%。在出生后第 7 天（PND），尿道下裂大鼠的 GT 中观察到雄激素受体（AR）和 FGF8 的 mRNA 和蛋白表达水平降低。在显示尿道下裂的组中观察到血清睾酮（T）水平降低，这通过组织学分析得到了证实。使用数字摄影术进行的进一步解剖检查有助于揭示与尿道下裂密切相关的器官发育不良的可视化表达。此外，还记录了体重（BW）和肛生殖器距离（AGD）的变化，显示出明确的减少。总的来说，这些数据清楚地表明雄激素和 FGF8 之间存在相互作用，这可能在 DBP 诱导的尿道下裂和异常器官发育中发挥重要作用。
