宫内抗雄性物质对胎鼠及新生大鼠阴茎组织Bax和Bcl-2表达的影响

Intra-amniotic androgen disruption exposure on the expression of transcriptional level of Bax and Bcl-2 in embryo and preterm rat genital tissues

目的:观察宫内抗雄性物质对胎鼠及新生大鼠阴茎组织Bax和Bcl-2基因表达的影响,探讨其与尿道下裂发病机制之间的关系。方法:定期受孕SD大鼠随机分为氟他胺(Flutamide,Flu)组和生理盐水组(对照组),于孕12～16d每天分别腹部皮下注射Flu/生理盐水100mg/(kg·d),两组动物均于胚胎19d及出生后第1、4、7d各随机取8只,应用反转录-聚合酶链反应技术检测各组阴茎组织Bax和Bcl-2基因的表达。结果:对照组bax基因的表达在孕19d～生后1d(GD19～PND1)随鼠龄增加表达逐渐增强,至PND1表达最强,以后逐渐减弱。Flu组在GD19～PND4均较对照组表达增强,且在END19和PND1与对照组相比,差异具有统计学意义。Flu组bcl-2mRNA表达在GD19～PND7均较对照组强,且在PND4和PND7与对照组相比,差异有统计学意义。结论:宫内抗雄性物质可能通过调控bax/bcl-2基因的表达,引起阴茎组织细胞异常凋亡,尿道板腔化受阻,进而导致尿道下裂的发生。

Objective To investigate the expression of bax and bcl-2 mRNA in genital tissues of embryo and preterm rats exposed to intra-amniotic androgen disruption and to elucidate the relationship between intrauterine androgen disruption and the pathogenesis of hypospadias. Methods Timed pregnant Sprague Dawley rats were randomly divided into two groups： Normal saline group and Flutamide group. Normal saline or Flutamide were injected into the rats on gestational days 12 through 16, respectively. The genital tissues from groups aged gestational day 19 （GD19） and postnatal day 1 （PND1）, PND4, PND7 were removed. Bax mRNA and bcl-2mRNA levels were measured by semi-quantitative reverse transcription polymerase chain reaction （RT-PCR）. Results The levels of genital tissues mRNA content change of bax increased in control group while it decreased in Flutamide group from GD19 to PND7. However, in Flutamide group, it was significantly higher than controls from GD19 to PND1 in both group, and it has significant difference on PND4 and PND7 （P 〈 0.05）. Conclusions These results suggest Hutamide exposure induced overexpression of bax/bcl-2 is a potential bcause of apoptosis of genital ceils, and may contribute to the pathogenesy of hypospadias.