Islam Mohammed A, Hooiveld Guido J E J, van den Berg Johannes H J, van der Velpen Vera, Murk Albertinka J, Rietjens Ivonne M C M, van Leeuwen F X Rolaf
Division of Toxicology, Wageningen University, Stippeneng 4, 6708 WE Wageningen, the Netherlands.
Department of Agricultural Chemistry, Sher-e-Bangla Agricultural University, Dhaka, Bangladesh.
Toxicol Rep. 2018 Oct 24;5:1087-1097. doi: 10.1016/j.toxrep.2018.10.012. eCollection 2018.
This toxicogenomic study was conducted to predict (post)menopausal human health effects of commercial soy supplementation using ovariectomized rats as a model. Different target tissues (i.e. breast, uterus and sternum) and non-target tissues (i.e. peripheral blood mononuclear cells (PBMC), adipose and liver) of ovariectomized F344 rats exposed to a commercially available soy supplement for eight weeks, were investigated. Changes in gene expression in these tissues were analysed using whole-genome microarray analysis. No correlation in changes in gene expression were observed among different tissues, indicating tissue specific effects of soy isoflavone supplementation. Out of 87 well-established estrogen responsive genes (ERGs), only 19 were found to be significantly regulated (p < 0.05) in different tissues, particularly in liver, adipose and uterus tissues. Surprisingly, no ERGs were significantly regulated in estrogen sensitive breast and sternum tissues. The changes in gene expression in PBMC and adipose tissue in rats were compared with those in (post)menopausal female volunteers who received the same supplement in a similar oral dose and exposure duration in human intervention studies. No correlation in changes in gene expression between rats and humans was observed. Although receiving a similar dose, in humans the plasma levels expressed as total free aglycones were several folds higher than in the rat. Therefore, the overall results in young ovariectomized female F344 rats indicated that using rat transcriptomic data does not provide a suitable model for human risk or benefit analysis of soy isoflavone supplementation.
本毒理基因组学研究旨在以去卵巢大鼠为模型，预测商业大豆补充剂对绝经（前/后）期人类健康的影响。研究了八周内暴露于市售大豆补充剂的去卵巢F344大鼠的不同靶组织（即乳腺、子宫和胸骨）和非靶组织（即外周血单核细胞（PBMC）、脂肪组织和肝脏）。使用全基因组微阵列分析这些组织中的基因表达变化。不同组织间未观察到基因表达变化的相关性，表明大豆异黄酮补充剂具有组织特异性效应。在87个已确立的雌激素反应基因（ERGs）中，仅发现19个在不同组织中受到显著调控（p < 0.05），特别是在肝脏、脂肪组织和子宫组织中。令人惊讶的是，雌激素敏感的乳腺和胸骨组织中没有ERGs受到显著调控。将大鼠PBMC和脂肪组织中的基因表达变化与人类干预研究中接受相同补充剂、相似口服剂量和暴露持续时间的绝经（前/后）期女性志愿者的基因表达变化进行了比较。未观察到大鼠和人类基因表达变化的相关性。尽管接受了相似剂量，但人类血浆中以总游离苷元表示的水平比大鼠高几倍。因此，年轻去卵巢雌性F344大鼠的总体结果表明，使用大鼠转录组数据不能为大豆异黄酮补充剂的人类风险或益处分析提供合适的模型。
