Ikeda Masahiko, Tamura Masashi, Yamashita Junko, Suzuki Chinatsu, Tomita Takako
University of Shizuoka, Graduate School of Nutritional and Environmental Sciences, 52-1, Yada, Shizuoka 422 8526, Japan.
Toxicol Appl Pharmacol. 2005 Aug 15;206(3):351-5. doi: 10.1016/j.taap.2004.11.019.
The effects of in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the reproductive system of male rat offspring (F1) and the sex ratio of the subsequent generation (F2) were examined. Female Holtzman rats were gavaged with an initial loading dose of 400 ng/kg TCDD prior to mating, followed by weekly maintenance doses of 80 ng/kg during mating, pregnancy, and the lactation period. Maternal exposure to TCDD had no significant effects on fetus/pup (F1) mortality, litter size, or sex ratio on gestation day (GD) 20 or postnatal day (PND) 2. The TCDD concentration in maternal livers and adipose tissue on GD20 was 1.21 and 1.81 ng/kg, respectively, and decreased at weaning to 0.72 in the liver and 0.84 in the adipose tissue. In contrast, the TCDD concentration in pup livers was 1.32 ng/kg on PND2 and increased to 1.80 ng/kg at weaning. Ventral prostate weight of male offspring was significantly decreased by TCDD exposure on PND28 and 120 compared with that of controls. Weight of the testes, cauda epididymides, and seminal vesicle, and sperm number in the cauda epididymis were not changed by TCDD exposure at PND120. TCDD- or vehicle-exposed male offspring were mated with unexposed females. The sex ratio (percentage of male pups) of F2 offspring was significantly reduced in the TCDD-exposed group compared with controls. These results suggest that in utero and lactational TCDD exposures affect the development of male gonads in offspring (F1), leading to changes in the sex ratio of the subsequent generation (F2).
研究了子宫内和哺乳期暴露于2,3,7,8-四氯二苯并对二恶英（TCDD）对雄性大鼠后代（F1）生殖系统以及后续代（F2）性别比的影响。雌性Holtzman大鼠在交配前经口灌胃给予初始负荷剂量400 ng/kg TCDD，随后在交配、怀孕和哺乳期每周给予维持剂量80 ng/kg。母体暴露于TCDD对胎儿/幼崽（F1）死亡率、窝仔数或妊娠第20天（GD20）或出生后第2天（PND2）的性别比没有显著影响。GD20时母体肝脏和脂肪组织中的TCDD浓度分别为1.21和1.81 ng/kg，断奶时肝脏中降至0.72 ng/kg，脂肪组织中降至0.84 ng/kg。相比之下，幼崽肝脏中的TCDD浓度在PND2时为1.32 ng/kg，断奶时增加到1.80 ng/kg。与对照组相比，TCDD暴露使雄性后代在PND28和120时的腹侧前列腺重量显著降低。在PND120时，TCDD暴露对睾丸、附睾尾部和精囊的重量以及附睾尾部的精子数量没有影响。将暴露于TCDD或溶剂的雄性后代与未暴露的雌性交配。与对照组相比，TCDD暴露组F2后代的性别比（雄性幼崽百分比）显著降低。这些结果表明，子宫内和哺乳期暴露于TCDD会影响后代（F1）雄性性腺的发育，导致后续代（F2）性别比发生变化。
