怀孕小鼠高脂肪饮食,增加后3代乳腺癌风险
2017/07/08
“给怀孕小鼠喂食高脂肪饮食,会增加其三代子孙患乳腺癌的概率”。这是Georgetown Lombardi Comprehensive 癌症中心的研究团队发表在《Breast Cancer Research》期刊上的最新研究成果。研究负责人Leena Hilakivi-Clarke教授表示这一发现强调了孕妇饮食的研究重要性。


“给怀孕小鼠喂食高脂肪饮食,会增加其三代子孙患乳腺癌的概率”。

这是Georgetown Lombardi Comprehensive 癌症中心的研究团队发表在《Breast Cancer Research》期刊上的最新研究成果。研究负责人Leena Hilakivi-Clarke教授表示这一发现强调了孕妇饮食的研究重要性。

“我们认为,环境和生活方式(例如饮食)对于乳腺癌发生风险起着至关重要的作用。因此,我们通过动物模型揭示增加女性及其后代患癌风险的可能因素。” Hilakivi-Clarke解释道,“高脂肪饮食与炎症有关,许多流行病学研究已经证明炎症与癌症风险之间存在联系。”

Hilakivi-Clarke团队在早期的研究中发现,怀孕的小鼠食用高脂肪食物,生育下来的雌性后代患癌的概率会相对较高。现在,研究人员给怀孕10天的小鼠喂食高脂肪食物,这个时间胎儿卵巢内的卵细胞开始发育,相当于女性的怀孕中期。

结果再一次表明,怀孕的小鼠在妊娠中期开始食用高脂肪食物,会增加后代雌鼠罹患乳腺癌的概率。更重要的是,这种影响会持续3代。

基因测序结果显示,高脂肪饮食会引发后代遗传变异,具体包括与乳腺癌相关基因突变增加、癌症治疗的耐受力变强、癌症预后效果差以及抗肿瘤免疫力减弱。而且,相比于第一代,第三代小鼠发生遗传变异的概率增加了3倍!

参考资料:

High-fat diet in pregnancy increases breast cancer risk over generations in animal study

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  • Maternal intake of high n-6 polyunsaturated fatty acid diet during pregnancy causes transgenerational increase in mammary cancer risk in mice

    Background Maternal and paternal high-fat (HF) diet intake before and/or during pregnancy increases mammary cancer risk in several preclinical models. We studied if maternal consumption of a HF diet that began at a time when the fetal primordial germ cells travel to the genital ridge and start differentiating into germ cells would result in a transgenerational inheritance of increased mammary cancer risk. Methods Pregnant C57BL/6NTac mouse dams were fed either a control AIN93G or isocaloric HF diet composed of corn oil high in n-6 polyunsaturated fatty acids between gestational days 10 and 20. Offspring in subsequent F1–F3 generations were fed only the control diet. Results Mammary tumor incidence induced by 7,12-dimethylbenz[a]anthracene was significantly higher in F1 (p < 0.016) and F3 generation offspring of HF diet-fed dams (p < 0.040) than in the control offspring. Further, tumor latency was significantly shorter (p < 0.028) and burden higher (p < 0.027) in F1 generation HF offspring, and similar trends were seen in F3 generation HF offspring. RNA sequencing was done on normal mammary glands to identify signaling differences that may predispose to increased breast cancer risk by maternal HF intake. Analysis revealed 1587 and 4423 differentially expressed genes between HF and control offspring in F1 and F3 generations, respectively, of which 48 genes were similarly altered in both generations. Quantitative real-time polymerase chain reaction analysis validated 13 chosen up- and downregulated genes in F3 HF offspring, but only downregulated genes in F1 HF offspring. Ingenuity Pathway Analysis identified upregulation of Notch signaling as a key alteration in HF offspring. Further, knowledge-fused differential dependency network analysis identified ten node genes that in the HF offspring were uniquely connected to genes linked to increased cancer risk (ANKEF1, IGFBP6, SEMA5B), increased resistance to cancer treatments (SLC26A3), poor prognosis (ID4, JAM3, TBX2), and impaired anticancer immunity (EGR3, ZBP1). Conclusions We conclude that maternal HF diet intake during pregnancy induces a transgenerational increase in offspring mammary cancer risk in mice. The mechanisms of inheritance in the F3 generation may be different from the F1 generation because significantly more changes were seen in the transcriptome.

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