2,3,7,8-tetrachlorodibenzo-p-dioxin interacts with endogenous estradiol to disrupt prostate gland morphogenesis in male rat fetuses.
2,3,7,8-tetrachlorodibenzo-p-dioxin interacts with endogenous estradiol to disrupt prostate gland morphogenesis in male rat fetuses.
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2,3,7,8-四氯二苯并-p-二恶英与内源性雌二醇相互作用，破坏雄性大鼠胎儿的前列腺形态发生。
DOI：
10.1093/toxsci/67.2.264
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
vomSaal,FrederickS
中科院分区：
文献类型：
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作者：
Timms,BarryG;Peterson,RichardE;vomSaal,FrederickS
胎儿暴露于2,3,7,8-四氯二苯并-对二恶英（TCDD）会干扰大鼠和小鼠雄性生殖系统的正常发育。我们研究了TCDD对妊娠第20天雄性大鼠胎儿泌尿生殖系统（尿道、前列腺和精囊）初始发育的影响。计算机辅助三维重建测定前列腺芽数、前列腺大小及精囊大小。妊娠大鼠在妊娠第15天给予TCDD单次口服（1 μg/kg）。根据相邻胎儿性别确定男性胎儿宫内位（IUP）： 2F名男性位于2名女性之间，2M名男性位于2名男性之间。对照组2F男性血清雌二醇升高，前列腺增大，对照组2M男性血清睾酮升高，精囊增大，证实了先前的发现。TCDD对血清睾酮无明显影响。仅在2F男性中，TCDD显著降低了泌尿生殖窦背颅和背外侧区域的芽数和前列腺的总体大小，并与血清雌二醇的显著降低有关。相比之下，在2万名男性中，血清雌二醇和前列腺相同区域的前列腺芽的数量和大小都没有受到TCDD的影响，尽管精囊大小减小了。这些发现表明，性腺类固醇水平的个体差异影响了男性胎儿发育中的前列腺对TCDD的反应。此外，这些TCDD效应可能部分由血清雌二醇水平降低介导。
Fetal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) interferes with normal development of the male reproductive system in rats and mice. We examined the effects of TCDD on the initial development of the urogenital system (urethra, prostate, and seminal vesicles) in male rat fetuses on gestation day (GD) 20. The number of prostatic buds and size of prostate glands as well as seminal vesicle size was determined by computer-assisted 3D reconstruction. Pregnant Holtzman rats received a single oral dose of TCDD (1 μg/kg) on GD 15. The intrauterine position (IUP) of male fetuses was identified based on the sex of adjacent fetuses: 2F males were located between 2 females and 2M males were located between 2 males. Control 2F males had elevated serum estradiol and larger prostates than control 2M males, which had elevated serum testosterone and larger seminal vesicles, confirming prior findings. There was no effect of TCDD on serum testosterone. TCDD significantly decreased the number of buds in the dorsocranial and dorsolateral regions of the urogenital sinus and overall prostate size, and was associated with a significant decrease in serum estradiol only in 2F males. In contrast, in 2M males both serum estradiol and the number and size of prostatic buds in these same regions of the prostate were unaffected by TCDD, although seminal vesicle size was reduced. These findings show that individual differences in gonadal steroid levels influence the response of the developing prostate to TCDD in male fetuses. In addition, these TCDD effects may be mediated in part by a decrease in serum estradiol levels.