Critical window of male reproductive tract development in rats following gestational exposure to di-n-butyl phthalate
Critical window of male reproductive tract development in rats following gestational exposure to di-n-butyl phthalate
复制标题
DOI：
10.1002/bdrb.20050
复制
发表时间：
2005-06-01
影响因子：
--
通讯作者：
Foster, PMD
中科院分区：
文献类型：
--
作者：
Carruthers, CM;Foster, PMD
背景：妊娠期暴露于邻苯二甲酸二丁酯（DBP），一种普遍存在的环境污染物，已被证明通过抗雄激素的作用干扰男性生殖道的发育。这项研究是为了确定男性生殖道，特别是睾丸和附睾异常发育的关键日子。方法：分别于妊娠第14、15、15、16、17、17、18、19、19、20天（妊娠第0天）给药500 mg/kg/d。在产后第1天和第13天测量肛门生殖器距离（AGD），仅在产后第13天记录肛门生殖器距离（AGD）。断奶后，雄性被允许成熟到PND 90，那时它们被尸检。记录Areloa数和AGD，并称重睾丸、附睾、精囊、前列腺、肾脏和肝脏。采集血清，测定总睾酮浓度。结果：对产仔数、性别比、血清睾酮浓度或幼崽死亡率均无明显影响。在妊娠第15和16天或妊娠第18和19天产前暴露于DBP的男性中，AGD的永久性降低具有统计学意义。在产后13天，暴露于DBP的男性在产后15和16、16和17、17和18、19和20天出现乳晕。然而，在第16和17天DBP暴露后，只有患病的雄性出现永久性滞留。仅在妊娠第17和18天暴露于DBP可引起附睾重量的减少；而仅暴露在GD 16和GD 17上，由于水肿，睾丸重量显著增加。在本研究中，在妊娠期暴露于DBP后，附睾和睾丸畸形最为普遍。仅在妊娠第16和17天，dbp暴露雄性的附睾畸形显著增加，其特征是各区域发育不全，睾丸小或松弛。结论：上述结果提示，暴露于DBP 2 d对男性胎儿生殖道发育非常有害，异常发育的关键窗口期为GD 16-18。
BACKGROUND: Gestational exposure to di-n-butyl phthalate (DBP), a ubiquitous environmental contaminant, has been shown to interfere with the development of the male reproductive tract by acting as an antiandrogen. This study was conducted to identify the critical days for the abnormal development of the male reproductive tract, specifically the testis and epididymis. METHODS: Timed-pregnant Sprague-Dawley rats were dosed with DBP at 500 mg/kg/day on gestation day (GD) 14 and 15, 15 and 16, 16 and 17,17 and 18, 18 and 19, or 19 and 20 (GD 0 = plug day). Anogenital distance (AGD) was measured on postnatal day (PND) 1 and 13, while areloa number was recorded on PND 13 only. After weaning, males were allowed to mature to PND 90 at which time they were necropsied. Areloa number and AGD were recorded and testes, epididymides, seminal vesicles, prostate gland, kidneys, and liver weighed. Blood serum was collected and assayed for total testosterone concentration. RESULTS: There were no observable effects on litter size, sex ratio, serum testosterone concentration, or mortality of pups. Statistically significant permanent reductions in AGD were seen in males exposed prenatally to DBP on GD 15 and 16 or GD 18 and 19. On PND 13, areola were present in males exposed to DBP on GD 15 and 16, 16 and 17, 17 and 18, and 19 and 20. However, permanent retention occurred only ill males after DBP exposure on GD 16 and 17. Exposure to DBP on only GD 17 and 18 elicited a reduction in epididymal weights; while exposure on only GD 16 and 17 caused a significant increase in the weights of the testes due to edema. In this study, epididymal and testicular malformations were most prevalent after exposure to DBP on any gestational day. Epididymal malformations, characterized by agenesis of various regions and small or flaccid testes were significantly increased in DBP-exposed males only on GD 16 and 17. CONCLUSIONS: These findings suggest that 2-day DBP exposure is highly detrimental to the developing reproductive tract of the male fetus and the critical window for abnormal development is GD 16-18.