INUTERO AND LACTATIONAL EXPOSURE OF MALE-RATS TO 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN .1. EFFECTS ON ANDROGENIC STATUS
INUTERO AND LACTATIONAL EXPOSURE OF MALE-RATS TO 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN .1. EFFECTS ON ANDROGENIC STATUS
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DOI：
10.1016/0041-008x(92)90101-w
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发表时间：
1992-05-01
影响因子：
3.8
通讯作者：
PETERSON, RE
中科院分区：
文献类型：
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作者：
MABLY, TA;MOORE, RW;PETERSON, RE
2,3,7,8-四氯二苯并-对二恶英（TCDD）以明显毒性剂量施用于青春期后大鼠时，会对雄性生殖系统产生各种不良影响，包括血浆雄激素浓度降低。如果这种雄激素缺乏在产前和/或产后早期产生，它可能通过破坏性器官的发育和/或导致中枢神经系统的不完全性别分化而潜在地损害男性生殖功能。为了确定TCDD是否会降低围产期雄激素浓度和/或损害雄激素依赖性的围产期发育，在妊娠第15天给妊娠大鼠1.0 μg TCDD/kg或对照药。妊娠第18 ~ 21天，TCDD显著降低了雄性胎儿血浆睾酮浓度。出生后不久血浆睾酮浓度的激增也显著减少，正如肛门生殖器距离，一个雄激素依赖的参数。为了进一步研究围产期TCDD暴露对雄性生殖系统的影响，我们在妊娠第15天以TCDD（0.064、0.16、0.40或1.0 μ/kg, po）或对照剂的剂量对所生的大鼠进行了从出生到性成熟的评估。本报告描述了它们的生长、身体发育和雄激素状态（即雄激素浓度和雄激素依赖的结构和功能）；对精子发生、睾丸组织学、性行为和生育能力的影响分别报道。几乎没有证据表明TCDD会导致母体中毒。后代明显毒性的迹象仅限于活产减少8%（仅最高剂量），体重增加和饲料消耗减少（仅两次最高剂量），这些在成年早期消失。在雄激素状态方面，母体TCDD剂量低至0.16 μg/kg，可显著降低1日龄和4日龄雄性的肛门生殖器距离，延缓睾丸下降，降低精囊和前列腺腹侧重量。在幼龄、青春期、青春期后和性成熟阶段观察到器官重量的减少。血浆睾酮和5α-二氢睾酮浓度在这些时候趋于降低（尽管不是很明显），而血浆黄体生成素浓度通常不受影响。总的来说，这些结果表明，围产期暴露于TCDD会改变雄鼠从胎儿期到成年期的雄激素状态，TCDD可以影响雄激素状态，但不会引起明显的毒性。在大鼠中，雄性生殖系统似乎比迄今为止研究的任何其他器官或器官系统对子宫内和哺乳期接触TCDD的毒性作用更敏感。
When administered in overtly toxic doses to postpubescent rats, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces a variety of adverse effects on the male reproductive system including a decrease in plasma androgen concentrations. If such an androgenic deficiency were produced prenatally and/or early postanatally it could potentially impair male reproductive function by disrupting the development of sex organs and/or causing incomplete sexual differentiation of the central nervous system. To determine whether TCDD can reduce androgen concentrations perinatally and/or impair androgen-dependent perinatal development, pregnant Holtzman rats were treated with 1.0 μg TCDD/kg or vehicle on Day 15 of gestation. Plasma testosterone concentrations in fetal males were significantly reduced by TCDD on Gestation Days 18 through 21. The surge in plasma testosterone concentrations shortly after birth was also significantly reduced, as was anogenital distance, an androgen-dependent parameter. To further investigate the effects of perinatal TCDD exposure on the male reproductive system, rats born to dams given TCDD (0.064, 0.16, 0.40, or 1.0 μ/kg, po) or vehicle on Day 15 of gestation were evaluated from birth through sexual maturation. This report describes their growth, physical development, and androgenic status (i.e., androgen concentrations and androgen-dependent structures and functions); effects on spermatogenesis, testicular histology, sexual behavior, and fertility are reported separately. There was little evidence that TCDD caused maternal toxicity. Signs of overt toxicity in offspring were limited to an 8% reduction in live births (highest dose only) and to decreases in body weight gain and feed consumption (two highest doses only) which disappeared by early adulthood. With respect to androgenic status, maternal TCDD doses as low as 0.16 μg/kg produced significant dose-related decreases in the anogenital distance of 1- and 4-day-old males, delays in testicular descent, and decreases in seminal vesicle and ventral prostate weights. The reductions in organ weights were observed when rats were at the juvenile, pubertal, postpubertal, and mature stages of sexual development. Plasma testosterone and 5α-dihydrotestosterone concentrations tended to be reduced at these times (though not significantly), while plasma luteinizing hormone concentrations were generally unaffected. Collectively, these results demonstrate that perinatal TCDD exposure alters the androgenic status of male rats from the fetal stage into adulthood, and that TCDD can affect androgenic status without causing overt toxicity. In rats, the male reproductive system appears to be more sensitive to the toxic effects of in utero and lactational TCDD exposure than any other organ or organ system studied thus far.