Tissue Distribution of Methylmercury in Obese Pregnant Mice and Fetuses

IF 2.7 4区 医学 Q3 TOXICOLOGY
Megumi Yamamoto, Chisato Kataoka, Rie Yanagisawa, Tomoharu Yokooji, Eiji Shibata, Mayumi Tsuji, Toshihide Sakuragi, Masahisa Horiuchi, Masaaki Nakamura, Mineshi Sakamoto
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Abstract

Despite the high frequency of pregnancies complicated by abnormal glucose metabolism associated with obesity, methylmercury (MeHg) metabolism in pregnant women with abnormal glucose metabolism is unclear. We aimed to elucidate the MeHg tissue distribution in obese female mice with abnormal glucose metabolism and their fetuses. Female C57BL/6J mice were fed a high-fat diet (HFD) or a standard diet (Ctrl) for 12 weeks and mated. HFD mice showed mild glucose metabolism abnormalities as assessed by an oral glucose tolerance test. Maternal tissues (brain, liver, and kidney) and blood (plasma and blood cells) and fetal tissues (brain, liver, kidney, and placenta) were collected from these mice 24 h after oral administration of MeHg (a single dose of 1 or 5 mg Hg/kg) on Day 16 of mating. The total mercury level was determined in each sample, and its distribution to each tissue was estimated using Kp values (total mercury in each tissue/total mercury in maternal plasma). The Kp values for the maternal brain and liver were lower in HFD mice than in Ctrl mice, but no significant difference between groups was observed in the kidney or blood cells. The Kp values for all fetal tissues were lower in HFD mice than in Ctrl mice. Pregnant mice showed higher Kp values for the brain and lower Kp values for the kidney than those in nonpregnant mice, regardless of diet. These results will provide useful information to assess the risk of MeHg in obese mothers with glucose metabolism abnormalities and their fetuses.

甲基汞在肥胖妊娠小鼠和胎儿的组织分布。
尽管妊娠合并糖代谢异常与肥胖相关的发生率很高,但糖代谢异常孕妇的甲基汞(MeHg)代谢情况尚不清楚。我们旨在阐明糖代谢异常的肥胖雌性小鼠及其胎儿MeHg的组织分布。雌性C57BL/6J小鼠分别饲喂高脂饲粮(HFD)和标准饲粮(Ctrl) 12周后进行交配。通过口服葡萄糖耐量试验评估,HFD小鼠表现出轻度葡萄糖代谢异常。在交配第16天口服MeHg(单剂量1或5 mg Hg/kg) 24小时后,收集这些小鼠的母体组织(脑、肝和肾)、血液(血浆和血细胞)和胎儿组织(脑、肝、肾和胎盘)。确定了每个样品中的总汞水平,并使用Kp值(每个组织中的总汞/母体血浆中的总汞)估计其在每个组织中的分布。HFD小鼠母体脑和肝脏的Kp值低于对照组小鼠,但肾脏和血细胞的Kp值组间无显著差异。HFD小鼠各胎组织的Kp值均低于对照组小鼠。与未怀孕的小鼠相比,怀孕小鼠的大脑Kp值更高,肾脏Kp值更低,与饮食无关。这些结果将为评估糖代谢异常的肥胖母亲及其胎儿MeHg的风险提供有用的信息。
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来源期刊
CiteScore
7.00
自引率
6.10%
发文量
145
审稿时长
1 months
期刊介绍: Journal of Applied Toxicology publishes peer-reviewed original reviews and hypothesis-driven research articles on mechanistic, fundamental and applied research relating to the toxicity of drugs and chemicals at the molecular, cellular, tissue, target organ and whole body level in vivo (by all relevant routes of exposure) and in vitro / ex vivo. All aspects of toxicology are covered (including but not limited to nanotoxicology, genomics and proteomics, teratogenesis, carcinogenesis, mutagenesis, reproductive and endocrine toxicology, toxicopathology, target organ toxicity, systems toxicity (eg immunotoxicity), neurobehavioral toxicology, mechanistic studies, biochemical and molecular toxicology, novel biomarkers, pharmacokinetics/PBPK, risk assessment and environmental health studies) and emphasis is given to papers of clear application to human health, and/or advance mechanistic understanding and/or provide significant contributions and impact to their field.
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