Won Sae Bom, Han Anna, Kwon Young Hye
Department of Food and Nutrition, Seoul National University, Seoul 08826, Republic of Korea.
Department of Food and Nutrition, Seoul National University, Seoul 08826, Republic of Korea; Research Institute of Human Ecology, Seoul National University, Seoul 08826, Republic of Korea.
J Nutr Biochem. 2017 Apr;42:51-61. doi: 10.1016/j.jnutbio.2016.12.013. Epub 2017 Jan 12.
In utero environment is known to affect fetal development. Especially, the distinct fetal programming of carcinogenesis was reported in offspring exposed to maternal diets containing soy protein isolate (SPI) or genistein. Therefore, we investigated whether maternal consumption of low-isoflavone SPI or genistein alters hepatic gene expression and liver development in rat offspring. Female Sprague-Dawley rats were fed a casein diet, a low-isoflavone SPI diet or a casein diet supplemented with genistein (250 mg/kg diet) for 2 weeks before mating and throughout pregnancy and lactation. Male offspring were studied on postnatal day 21 (CAS, SPI and GEN groups). Among 965 differentially expressed hepatic genes related to maternal diet (P<.05), the expression of 590 was significantly different between CAS and SPI groups. Conversely, the expression of 88 genes was significantly different between CAS and GEN groups. Especially, genes involved in drug metabolism were significantly affected by the maternal diet. SPI group showed increased cell proliferation, reduced apoptosis and activation of the mTOR pathway, which may contribute to a higher relative liver weight compared to other groups. We observed higher serum homocysteine levels and lower global and CpG site-specific DNA methylation of Gadd45b, a gene involved in cell proliferation and apoptosis, in SPI group compared to CAS group. Maternal SPI diet also reduced histone H3-Lysine 9 (H3K9) trimethylation and increased H3K9 acetylation in offspring. These results demonstrate that maternal consumption of a low-isoflavone SPI diet alters the hepatic gene expression profile and liver development in offspring possibly by epigenetic processes.
已知子宫内环境会影响胎儿发育。特别是，有报道称，暴露于含大豆分离蛋白（SPI）或染料木黄酮的母体饮食中的后代会出现独特的致癌胎儿编程。因此，我们研究了母体摄入低异黄酮SPI或染料木黄酮是否会改变大鼠后代的肝脏基因表达和肝脏发育。在交配前2周以及整个怀孕和哺乳期，给雌性Sprague-Dawley大鼠喂食酪蛋白饮食、低异黄酮SPI饮食或补充了染料木黄酮（250毫克/千克饮食）的酪蛋白饮食。对出生后第21天的雄性后代进行研究（CAS、SPI和GEN组）。在与母体饮食相关的965个差异表达的肝脏基因中（P<0.05），CAS组和SPI组之间有590个基因的表达存在显著差异。相反，CAS组和GEN组之间有88个基因的表达存在显著差异。特别是，参与药物代谢的基因受到母体饮食的显著影响。SPI组显示细胞增殖增加、凋亡减少以及mTOR途径激活，这可能导致其相对肝脏重量高于其他组。与CAS组相比，我们观察到SPI组血清同型半胱氨酸水平较高，而参与细胞增殖和凋亡的基因Gadd45b的整体和CpG位点特异性DNA甲基化较低。母体SPI饮食还降低了后代组蛋白H3-赖氨酸9（H3K9）的三甲基化水平，并增加了H3K9的乙酰化水平。这些结果表明，母体摄入低异黄酮SPI饮食可能通过表观遗传过程改变后代的肝脏基因表达谱和肝脏发育。
