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子宫内暴露于4-羟基-2,3,3',4',5-五氯联苯(4-OH-CB107)对大鼠发育里程碑、类固醇激素水平及雌性发情周期的影响。

Effects of in utero exposure to 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) on developmental landmarks, steroid hormone levels, and female estrous cyclicity in rats.

作者信息

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

机构信息

Toxicology Group, Wageningen University, Wageningen, The Netherlands.

出版信息

Toxicol Sci. 2004 Nov;82(1):259-67. doi: 10.1093/toxsci/kfh251. Epub 2004 Aug 13.

Abstract

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.

摘要

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。

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