Interactive effects of TCDD and p,p′-DDE on male reproductive tract development in in utero and lactationally exposed rats
Interactive effects of TCDD and p,p′-DDE on male reproductive tract development in in utero and lactationally exposed rats
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DOI：
10.1006/taap.1998.8572
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发表时间：
1999-01-01
影响因子：
3.8
通讯作者：
Peterson, RE
中科院分区：
文献类型：
--
作者：
Loeffler, IK;Peterson, RE
发育中的雄性大鼠生殖系统对低剂量的TCDD和p，p '-DDE（DDE）高度敏感，它们通过不同的机制发挥抗雄激素作用。本研究调查了子宫内和哺乳期暴露于这些化合物的混合物的相互作用。妊娠Holtzman大鼠接受以下药物之一：在妊娠第14-18天给予溶剂，在妊娠第15天给予0.25 μ g/kg TCDD，在妊娠第14-18天给予100 mg/kg DDE，或在妊娠第15天给予0.25 μ g/kg TCDD，在妊娠第14-18天给予100 mg/kg DDE。在出生后第21天（断奶）、PND 32天（青春期前）、PND 49天（青春期）和PND 63天（青春期后）对雄性后代实施人道处死。这些剂量的TCDD和DDE的共同管理，以加强他们的个人行动对前列腺重量PND 21，而前列腺雄激素受体的免疫染色表现出的模式特征的影响，这两种化合物单独。附睾尾部精子数量减少，每种化合物，但没有进一步减少暴露于TCDD和DDE的组合。在较高剂量的两种化合物下，肛门生殖器距离、青春期开始时的年龄、每日精子产量、睾丸和附属性器官重量（非前列腺）以及前列腺雄激素调节基因转录物的水平受到影响，但在本研究中使用的剂量下不受影响。仅DDE给药动物在PND 13时保留乳头。治疗组间血清雄激素水平无差异。总之，发育中的大鼠前列腺是唯一敏感的TCDD和DDE的影响，这可能会增加彼此的影响，在这个器官。(C)北京：科学出版社.
The developing male rat reproductive system is highly sensitive to low doses of TCDD and p,p'-DDE (DDE), which exert antiandrogenic effects via different mechanisms. This study investigates the interactive effects of in utero and lactational exposure to a mixture of these compounds. Pregnant Holtzman rats received one of the following:, vehicle on gestation day (GD) 14-18, 0.25 mu g/kg TCDD on GD15, 100 mg/kg DDE on GD 14-18, or 0.25 mu g/kg TCDD on GD15 and 100 mg/kg DDE on GD 14-18. Male offspring were euthanized on postnatal day (PND) 21 (weaning), PND 32 (prepuberty), PND 49 (puberty), and PND 63 (post-puberty). Coadministration of these doses of TCDD and DDE appeared to potentiate their individual actions on prostate weight on PND 21, while immunostaining for the prostatic androgen receptor exhibited patterns characteristic of the effects of both compounds individually. Cauda epididymal sperm number was reduced by each compound but was not further reduced by exposure to TCDD and DDE in combination. Anogenital distance, age at onset of puberty, daily sperm production, testicular and accessory sex organ weight (nonprostate), and levels of prostatic androgen-regulated gene transcripts are affected at higher doses of both compounds, but not at the doses used in the present study. Only DDE-treated animals retained nipples on PND 13. Serum androgen levels did not differ between treatment groups. In conclusion, the developing rat prostate is uniquely sensitive to the effects of TCDD and DDE, which may augment one another's effects in this organ. (C) 1999 Academic Press.