Bjerke D L, Peterson R E
School of Pharmacy, University of Wisconsin, Madison 53706.
Toxicol Appl Pharmacol. 1994 Aug;127(2):241-9. doi: 10.1006/taap.1994.1158.
The male rat reproductive system is highly sensitive to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) when exposure occurs during fetal and neonatal development. Our objective was to determine the relative contributions of in utero versus lactational TCDD exposure to effects on male reproductive function. Pregnant Holtzman rats were treated on Day 15 of gestation with TCDD (1.0 micrograms/kg) or vehicle (control). At birth litters were standardized to five males and five females and fostered to dams of the same treatment or cross-fostered to dams of the opposite treatment. Four treatment groups were assessed: male offspring not exposed to TCDD by either route (control) and male offspring exposed to TCDD in utero (IU), via lactation (L), or in utero and via lactation (IUL). During early postnatal development, two androgen sensitive end points, relative anogenital distance and time to testis descent, were not affected by TCDD. However, end points evaluated later during development were altered. Time to separation of the prepuce from the glans penis (an index of pubertal development) was delayed, plasma testosterone concentrations and accessory sex organ weights were reduced, daily sperm production and epididymal sperm reserves were decreased, and sexual behavior was feminized. Certain responses were only produced by IU exposure whereas other responses only occurred following L exposure. Only IU TCDD exposure delayed pubertal development and decreased daily sperm production, while only L TCDD exposure feminized the sexual behavior of male offspring. For most male reproductive end points both IU and L TCDD exposure produced the same responses. Decreases in plasma testosterone concentrations, reductions in weights, protein, and DNA contents of ventral prostate and seminal vesicles, and decreases in epididymal sperm reserves were caused in young adult rats by either IU or L exposure to TCDD. We conclude that the route and timing of TCDD exposure during fetal and neonatal development of the rat determine the profile of male reproductive effects observed and that all effects in the present study, with the notable exception of feminized sexual behavior, can be caused by low level exposure to TCDD via the IU route alone.
在胎儿期和新生儿期发育期间暴露于2,3,7,8-四氯二苯并对二恶英（TCDD）时，雄性大鼠的生殖系统对其高度敏感。我们的目的是确定子宫内暴露与哺乳期暴露于TCDD对雄性生殖功能影响的相对作用。在妊娠第15天，给怀孕的霍尔茨曼大鼠用TCDD（1.0微克/千克）或赋形剂（对照）进行处理。出生时，将窝仔标准化为五只雄性和五只雌性，并寄养给相同处理的母鼠或交叉寄养给相反处理的母鼠。评估了四个处理组：未通过任何一种途径暴露于TCDD的雄性后代（对照）以及子宫内暴露于TCDD（IU）、通过哺乳期暴露于TCDD（L）或子宫内和通过哺乳期暴露于TCDD（IUL）的雄性后代。在出生后早期发育期间，两个雄激素敏感终点，即相对肛门生殖器距离和睾丸下降时间，不受TCDD影响。然而，在发育后期评估的终点发生了改变。包皮与阴茎头分离的时间（青春期发育的一个指标）延迟，血浆睾酮浓度和附属性腺器官重量降低，每日精子生成量和附睾精子储备减少，性行为出现雌性化。某些反应仅由子宫内暴露引起，而其他反应仅在哺乳期暴露后出现。仅子宫内暴露于TCDD会延迟青春期发育并减少每日精子生成量，而仅哺乳期暴露于TCDD会使雄性后代的性行为雌性化。对于大多数雄性生殖终点，子宫内和哺乳期暴露于TCDD都会产生相同的反应。子宫内或哺乳期暴露于TCDD会导致年轻成年大鼠血浆睾酮浓度降低、腹侧前列腺和精囊的重量、蛋白质和DNA含量减少以及附睾精子储备减少。我们得出结论，大鼠在胎儿期和新生儿期发育期间暴露于TCDD的途径和时间决定了所观察到的雄性生殖效应的特征，并且本研究中的所有效应，除了性行为雌性化这一显著例外，仅通过子宫内途径低水平暴露于TCDD即可引起。
