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对雄性长 Evans 带帽大鼠后代单次孕期剂量的 2,3,7,8-四氯二苯并对二恶英生殖效应的剂量反应分析。

A dose-response analysis of the reproductive effects of a single gestational dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin in male Long Evans Hooded rat offspring.

作者信息

Gray L E, Ostby J S, Kelce W R

机构信息

Reproductive Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.

出版信息

Toxicol Appl Pharmacol. 1997 Sep;146(1):11-20. doi: 10.1006/taap.1997.8223.

Abstract

Male rats exposed in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) display reduced fertility as a consequence of the direct action of TCDD on the epididymides, as well as delayed puberty and altered reproductive organ weights. The current study provides dose-response data for the reproductive effects of TCDD, administered during pregnancy, with an emphasis on the effects of TCDD on testicular, epididymal, and ejaculated sperm numbers. Long Evans Hooded rats were dosed by gavage with 0, 0.05, 0.20, or 0.80 microg TCDD/kg on Day 15 of gestation. After birth, growth, viability, and developmental landmarks were monitored in both male and female offspring. Shortly after puberty (49 and 63 days of age) and at 15 months of age, male offspring were necropsied. Growth and viability of the pups were reduced only at 0.80 microg TCDD/kg, eye opening was accelerated (all dosage groups), and puberty was delayed (at 0.20 and 0.80 microg TCDD/kg). Treated progeny displayed transient reductions in ventral prostate and seminal vesicle weights, while epididymal sperm reserves and glans penis size were permanently reduced. Ejaculated sperm numbers were reduced (45% in the 0.8 and by 25% in the 0.05 and 0.2 microg TCDD/kg dosage groups) to a greater degree than were cauda or caput/corpus epididymal or testicular (unaffected) sperm numbers. In conclusion, administration of TCDD on Day 15 of pregnancy at 0.05 microg/kg altered eye opening and reduced ejaculated sperm counts, while higher dosage levels also delayed puberty and permanently reduced cauda epididymal sperm reserves.

摘要

子宫内暴露于2,3,7,8-四氯二苯并对二恶英(TCDD)的雄性大鼠,由于TCDD对附睾的直接作用,生育能力降低,同时青春期延迟且生殖器官重量改变。本研究提供了孕期给予TCDD后生殖效应的剂量反应数据,重点关注TCDD对睾丸、附睾和射出精子数量的影响。在妊娠第15天,通过灌胃给Long Evans Hooded大鼠分别给予0、0.05、0.20或0.80微克TCDD/千克。出生后,对雄性和雌性后代的生长、活力和发育标志进行监测。在青春期后不久(49和63日龄)以及15月龄时,对雄性后代进行尸检。仅在0.80微克TCDD/千克剂量组幼崽的生长和活力降低,睁眼加速(所有剂量组),青春期延迟(0.20和0.80微克TCDD/千克剂量组)。处理后的子代腹侧前列腺和精囊重量短暂降低,而附睾精子储备和阴茎头大小永久降低。射出精子数量减少(0.8微克TCDD/千克剂量组减少45%,0.05和0.2微克TCDD/千克剂量组减少25%),其程度大于附睾尾部或附睾头/体部或睾丸(未受影响)的精子数量。总之,在妊娠第15天给予0.05微克/千克的TCDD会改变睁眼情况并减少射出精子数量,而更高剂量水平还会延迟青春期并永久减少附睾尾部精子储备。

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