Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland, USA.
Environ Toxicol Chem. 2013 Jun;32(6):1317-24. doi: 10.1002/etc.2179. Epub 2013 Apr 16.
Chicken (Gallus domesticus) embryonic exposure in ovo to a 58-congener polychlorinated biphenyl (PCB) mixture resulted in teratogenic heart defects in chick embryos at critical heart developmental stages Hamburger-Hamilton (HH) stages 10, 16, and 20. The 58-congener mixture contained relative proportions of primary congeners measured in belted sandpiper (Megaceryle alcyon) and spotted sandpiper (Actitis macularia) eggs collected along the upper Hudson River, New York, USA, and chicken doses were well below observed environmental exposure levels. Embryos were injected with 0.08 µg PCBs/g egg weight and 0.50 µg PCBs/g egg weight (0.01 and 0.064 ng toxic equivalent/g, respectively) at embryonic day 0, prior to incubation. Mortality of exposed embryos was increased at all developmental stages, with a marked rise in cardiomyopathies at HH16 and HH20 (p < 0.05). Heart abnormalities occurred across all treatments, including abnormal elongation and expansion of the heart tube at HH10, improper looping and orientation, indentations in the emerging ventricular wall (HH16 and HH20), and irregularities in overall heart shape (HH10, HH16, and HH20). Histology was conducted on 2 cardiac proteins critical to embryonic heart development, ventricular myosin heavy chain and titin, to investigate potential mechanistic effects of PCBs on heart development, but no difference was observed in spatiotemporal expression. Similarly, cellular apoptosis in the developing heart was not affected by exposure to the PCB mixture. Conversely, cardiomyocyte proliferation rates dramatically declined (p < 0.01) at HH16 and HH20 as PCB exposure concentrations increased. Early embryonic cardiomyocyte proliferation contributes to proper formation of the morphology and overall thickness of the ventricular wall. Therefore, in ovo exposure to this 58-congener PCB mixture at critical stages adversely affects embryonic heart development.
鸡(Gallus domesticus)胚胎在卵内暴露于 58 种同系多氯联苯(PCB)混合物中,导致鸡胚在关键心脏发育阶段 Hamburger-Hamilton(HH)阶段 10、16 和 20 出现致畸性心脏缺陷。58 种同系混合物包含在美国纽约州哈德逊河上游采集的带纹滨鹬(Megaceryle alcyon)和点斑滨鹬(Actitis macularia)卵中测量的主要同系物的相对比例,鸡胚的剂量远低于观察到的环境暴露水平。胚胎在孵化前的胚胎发育第 0 天以 0.08μg PCBs/g 卵重和 0.50μg PCBs/g 卵重(分别为 0.01 和 0.064ng 毒性当量/g)注射 PCBs。在所有发育阶段,暴露胚胎的死亡率均增加,在 HH16 和 HH20 时心肌病的发生率明显上升(p<0.05)。心脏异常发生在所有处理中,包括在 HH10 时心脏管的异常伸长和扩张、不当的环化和定向、出现的心室壁凹陷(HH16 和 HH20)以及整体心脏形状的不规则(HH10、HH16 和 HH20)。对心脏发育至关重要的 2 种心脏蛋白,即心室肌球蛋白重链和titin,进行了组织学检查,以研究 PCB 对心脏发育的潜在机制影响,但未观察到时空表达的差异。同样,发育中心脏的细胞凋亡也不受 PCB 混合物暴露的影响。相反,随着 PCB 暴露浓度的增加,HH16 和 HH20 时心肌细胞增殖率急剧下降(p<0.01)。早期胚胎心肌细胞增殖有助于心室壁形态和整体厚度的正常形成。因此,在关键阶段,这种 58 种同系 PCB 混合物的卵内暴露会对胚胎心脏发育产生不利影响。