Meerts Ilonka A T M, Hoving Saske, van den Berg Johannes H J, Weijers Bert M, Swarts Hans J, van der Beek Eline M, Bergman Ake, Koeman Jan H, Brouwer Abraham
Toxicology Group, Wageningen University, Wageningen, The Netherlands.
Toxicol Sci. 2004 Nov;82(1):259-67. doi: 10.1093/toxsci/kfh251. Epub 2004 Aug 13.
Previous studies have revealed that one of the major metabolites of PCBs detected in human blood, 4-OH-2,3,3',4',5-pentaCB (4-OH-CB107), accumulated in fetal liver, brain, and plasma and reduced maternal and fetal thyroid hormone levels after prenatal exposure to pregnant rats from gestational days (GD) 10-16. In the present study, the effects of 4-OH-CB-107 on developmental landmarks, steroid hormone levels, and estrous cyclicity of rat offspring after in utero exposure to 4-OH-CB107 was investigated. Pregnant rats were exposed to 0, 0.5, and 5.0 mg 4-OH-CB107 per kg bw from GD 10 to GD 16. Another group of rats was exposed to Aroclor 1254 (25 mg/kg bw) to study the differences between effects caused by parent PCB congeners and the 4-OH-CB107 alone. A significant, dose-dependent prolongation of the estrous cycle was observed in 75% and 82% of female offspring exposed to 0.5 and 5.0 mg 4-OH-PCB107, respectively, compared to 64% of Aroclor 1254 (25 mg/kg) exposed offspring. The diestrous stage of the estrous cycle was prolonged, resembling a state of pseudopregnancy, which might reflect early signs of reproductive senescence. Plasma estradiol concentrations in female rat offspring were significantly increased (50%) in the proestrous stage after exposure to 5 mg 4-OH-CB107 per kg bw. No effects on estradiol levels were observed in Aroclor 1254 treated animals. These results indicate that in utero exposure to 4-OH-CB107 leads to endocrine-disrupting effects, especially in female offspring. The possible impact on neurobehavior following exposure to 4-OH-CB107 will be reported elsewhere.
先前的研究表明,在人体血液中检测到的多氯联苯主要代谢物之一,4-羟基-2,3,3',4',5-五氯联苯(4-羟基-CB107),在胎肝、脑和血浆中蓄积,并在妊娠第10至16天对怀孕大鼠进行产前暴露后降低母体和胎儿的甲状腺激素水平。在本研究中,研究了子宫内暴露于4-羟基-CB-107后,4-羟基-CB-107对大鼠后代发育里程碑、类固醇激素水平和发情周期的影响。从妊娠第10天到第16天,给怀孕大鼠分别暴露于每千克体重0、0.5和5.0毫克的4-羟基-CB107。另一组大鼠暴露于艾氏剂1254(25毫克/千克体重),以研究母体多氯联苯同系物和单独的4-羟基-CB107所产生影响之间的差异。与暴露于艾氏剂1254(25毫克/千克)的后代中的64%相比,分别暴露于0.5和5.0毫克4-羟基-多氯联苯107的雌性后代中,有75%和82%观察到发情周期显著的剂量依赖性延长。发情周期的间情期延长,类似于假孕状态,这可能反映了生殖衰老的早期迹象。在每千克体重暴露于5毫克4-羟基-CB107后,雌性大鼠后代在发情前期的血浆雌二醇浓度显著增加(50%)。在艾氏剂1254处理的动物中未观察到对雌二醇水平的影响。这些结果表明,子宫内暴露于4-羟基-CB107会导致内分泌干扰效应,尤其是在雌性后代中。暴露于4-羟基-CB107后对神经行为的可能影响将在其他地方报道。