Gestational 1-nitropyrene exposure causes fetal growth restriction through disturbing placental vascularity and proliferation.
Gestational 1-nitropyrene exposure causes fetal growth restriction through disturbing placental vascularity and proliferation.
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DOI：
10.1016/j.chemosphere.2018.09.059
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发表时间：
2018-09
期刊：
影响因子：
8.8
通讯作者：
Ran Li;Xilu Wang;Bo Wang;Jian Li;Yaping Song;Biao Luo;Yuan-Hua Chen;Cheng Zhang;Hua Wang;De-xiang Xu
中科院分区：
文献类型：
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作者：
Ran Li;Xilu Wang;Bo Wang;Jian Li;Yaping Song;Biao Luo;Yuan-Hua Chen;Cheng Zhang;Hua Wang;De-xiang Xu
1-硝基芘（1-NP）是一种广泛存在于环境中的污染物，具有致突变性和致癌性。在这项研究中，我们评估了不同妊娠阶段暴露于1-NP对妊娠结局的影响。分别在孕早期（GD 1-GD 6）、孕中期（GD 7-GD 12）和孕晚期（GD 13-GD 17）每天通过灌胃给予妊娠小鼠1-NP。我们发现妊娠期1-NP暴露对每窝着床部位、早产和胎儿死亡没有影响。有趣的是，在妊娠晚期暴露于1-NP的小鼠显示出胎儿重量和顶臀长度的显著减少。相应地，胎盘重量和直径显着减少母鼠暴露于1-NP在妊娠后期。进一步的实验表明，孕晚期母体1-NP暴露以剂量依赖的方式减少胎盘绒毛膜区血窦面积。尽管妊娠期1-NP暴露对胎盘细胞凋亡的影响很小，但如通过TUNEL测定所确定的，在妊娠晚期暴露于1-NP的小鼠的胎盘绒毛膜区域中，Ki 67阳性细胞（细胞增殖的标志物）的比率降低。这些发现提供了证据表明，妊娠期1-NP暴露诱导胎儿生长受限的阶段依赖性的方式。胎盘是1-NP诱导胎儿生长受限过程中的毒性靶点。
1-Nitropyrene (1-NP) is a widely distributed pollutant in the environment and is best known for its mutagenicity and carcinogenicity. In this study, we evaluated the effects of 1-NP exposure in different gestational stages on the pregnant outcomes. Pregnant mice were administered with 1-NP by gavage daily in early (GD1-GD6), middle (GD7-GD12) or late pregnancy (GD13-GD17), respectively. We found that gestational 1-NP exposure had no effect on implantation sites per litter, preterm delivery and fetal death. Interestingly, mice exposed to 1-NP in late pregnancy showed a significant reduction in fetal weight and crown-rump length. Correspondingly, placental weight and diameter were markedly reduced in dams exposed to 1-NP in late pregnancy. Additional experiment showed maternal 1-NP exposure in late pregnancy reduced blood sinusoid area of placental labyrinthine region in a dose-dependent manner. Although gestational 1-NP exposure had little effect on placental cell apoptosis, as determined by the TUNEL assay, the rate of Ki67-positive cell, a marker of cell proliferation, was reduced in placental labyrinthine region of mice exposed to 1-NP in late pregnancy. These findings provide evidence that gestational 1-NP exposure induces fetal growth restriction in a stage-dependent manner. Placenta is a toxic target in the process of 1-NP-induced fetal growth restriction.