邻苯二甲酸二丁酯导致雄性大鼠子鼠尿道下裂畸形及其机制研究
发布时间：2018-08-21 09:49
【摘要】：目的:邻苯二甲酸二丁酯(DBP)孕晚期染毒诱导雄性SD大鼠子鼠发生尿道下裂畸形,并进一步探讨DBP致雄性子鼠发生尿道下裂的分子作用机制。方法:孕鼠20只,怀孕14~18 d,随机分为对照组和DBP染毒组,每天分别予大豆油及DBP 750 mg/kg灌胃。出生后(PND)1 d,统计雄性子鼠中尿道下裂的发生率,观察尿道下裂雄性子鼠生殖结节的病理学改变。放射免疫法检测血清雄激素水平,实时荧光定量PCR和Western印迹检测生殖结节中雄激素受体(AR)、音猬因子(Shh)、骨形态发生蛋白4(Bmp4)和成纤维细胞成长因子8(Fgf8)的mRNA和蛋白表达水平。结果:对照组中无尿道下裂发生,DBP染毒组中雄性子鼠尿道下裂发生率为43.6%,病理学检查发现生殖结节典型的尿道下裂畸形。尿道下裂雄性子鼠的血清雄激素水平[(0.49±0.05)ng/ml]较对照组[(1.12±0.05)ng/ml]明显降低(P0.05),生殖结节中AR、Shh、Bmp4和Fgf8基因的mRNA水平(0.50±0.05、0.65±0.07、0.42±0.05、0.46±0.04)较对照组(1.00±0.12、1.00±0.15、1.00±0.13、1.00±0.12)明显降低(P0.05),蛋白水平(0.34±0.05、0.51±0.07、0.43±0.05、0.57±0.04)较对照组(1.00±0.09、1.00±0.12、1.00±0.11、1.00±0.13)明显降低(P0.05)。结论:孕晚期DBP染毒可以导致雄性子鼠发生尿道下裂畸形。DBP通过降低雄性子鼠血清雄激素水平和生殖结节中AR、Shh、Bmp4、Fgf8基因的表达,影响生殖结节的正常发育,是DBP导致尿道下裂畸形发生的可能机制。
[Abstract]:Aim: to induce hypospadias in male SD rats induced by dibutyl phthalate (DBP) in late pregnancy and to explore the molecular mechanism of hypospadias induced by DBP. Methods: twenty pregnant rats were randomly divided into two groups: control group and DBP group. Soybean oil and DBP 750 mg/kg were administered daily. The incidence of hypospadias in male hypospadias and the pathological changes of reproductive nodules in male hypospadias were observed 1 day after (PND). Serum androgen levels were detected by radioimmunoassay and mRNA and protein expressions of androgen receptor (AR), sound hedgehog factor (Shh), (Bmp4) and fibroblast growth factor 8 (Fgf8) in reproductive nodules were detected by real-time fluorescence quantitative PCR and Western blotting. Results: there was no hypospadias in the control group. The incidence of hypospadias was 43.6 in the male hypospadias treated with DBP. The typical hypospadias deformity of reproductive nodules was found by pathological examination. 灏块亾涓嬭闆勬，
本文编号：2195332
[Abstract]:Aim: to induce hypospadias in male SD rats induced by dibutyl phthalate (DBP) in late pregnancy and to explore the molecular mechanism of hypospadias induced by DBP. Methods: twenty pregnant rats were randomly divided into two groups: control group and DBP group. Soybean oil and DBP 750 mg/kg were administered daily. The incidence of hypospadias in male hypospadias and the pathological changes of reproductive nodules in male hypospadias were observed 1 day after (PND). Serum androgen levels were detected by radioimmunoassay and mRNA and protein expressions of androgen receptor (AR), sound hedgehog factor (Shh), (Bmp4) and fibroblast growth factor 8 (Fgf8) in reproductive nodules were detected by real-time fluorescence quantitative PCR and Western blotting. Results: there was no hypospadias in the control group. The incidence of hypospadias was 43.6 in the male hypospadias treated with DBP. The typical hypospadias deformity of reproductive nodules was found by pathological examination. 灏块亾涓嬭闆勬，
本文编号：2195332
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