In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces genital dysmorphogenesis in the female rat
In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces genital dysmorphogenesis in the female rat
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DOI：
10.1006/taap.1997.8295
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发表时间：
1997-12-01
影响因子：
3.8
通讯作者：
Hirshfield, AN
中科院分区：
文献类型：
--
作者：
Flaws, JA;Sommer, RJ;Hirshfield, AN
最近，Gray和Ostby(Toxicol.APPL药水。133,285-294,1995)报告说，在子宫和哺乳期接触TCDD会导致大鼠雌性生殖系统的显著异常，包括生殖力和阴道线的减少。TCDD导致这种异常的机制尚不清楚。因此，我们试图确定：(1)TCDD是否通过破坏卵巢卵泡而降低生殖力；(2)阴道线是由于TCDD在胚胎发生期间导致的发育缺陷，还是由于青春期阴道异常开放造成的。于妊娠第11、15、18天给妊娠Holtzman大鼠灌胃1.0mgTCDD/kg或单次口服赋形剂，监测仔鼠阴道张口情况，分别于出生后第2、21、42天终止妊娠。切除生殖道，并评估其结构异常。并测定了每个卵巢的原始卵泡数。暴露于GD11、151或18的TCDD不改变阴道开放的日期，不影响卵巢形态，也不减少原始卵泡的数量。然而，在我们的研究中，这种暴露导致了最初由Gray和Ostby(1995)描述的阴蒂裂隙和阴道线，分别在大约55%-96%和36%-44%的窝窝中发生。组织学上，线条呈粗大的间充质，被上皮细胞包围。这种缺陷在出生时的组织切片上清晰可见，并在青春期前动物闭合的阴道中被注意到。这些数据表明，在子宫和哺乳期接触TCDD不会减少原始卵泡池的大小，但会导致阴道发育异常。(C)1997年学术出版社。
Recently, Gray and Ostby (Toxicol. Appl. Pharmacol. 133, 285-294, 1995) reported that in utero and lactational TCDD exposure causes striking abnormalities in the rat female reproductive system, including reduced fecundity and vaginal threads. The mechanism by which TCDD induces such abnormalities is unknown. Thus, we sought to determine: (1) whether TCDD reduced fecundity by destroying ovarian follicles and (2) whether the vaginal threads resulted from a TCDD-induced developmental defect during embryogenesis or abnormal vaginal opening at puberty. Pregnant Holtzman rats were treated with 1.0 mu g TCDD/kg or vehicle by a single oral dose on gestation day (GD) 11, 15, or 18. Female offspring were monitored for vaginal opening and terminated on postnatal days 2, 21, and 42. The reproductive tract was removed and evaluated for structural abnormalities. The number of primordial follicles also was determined for each ovary. TCDD exposure on GD 11, 151 or 18 did not change the day of vaginal opening, affect ovarian morphology, or reduce the number of primordial follicles. However, this exposure induced the cleft clitoris and vaginal thread originally described by Gray and Ostby (1995) in approximately 55-96% and 36-44% of the litters in our study, respectively. Histologically the thread presented as a thick cord of mesenchyme surrounded by epithelial cells. This defect was clearly visible in histological sections at birth and was noted in the closed vaginas of prepubertal animals. These data suggest that in utero and lactational exposure to TCDD does not reduce the size of the primordial follicle pool; however, it induces developmental abnormalities in the vaginal canal. (C) 1997 Academic Press.