Data from: Paternal B vitamin intake is a determinant of growth, hepatic lipid metabolism and intestinal tumor volume in female Apc1638N mouse offspring

Background
The importance of maternal nutrition to offspring health and risk of disease is well established. Emerging evidence suggests paternal diet may affect offspring health as well.
Objective
In the current study we sought to determine whether modulating pre-conception paternal B vitamin intake alters intestinal tumor formation in offspring. Additionally, we sought to identify potential mechanisms for the observed weight differential among offspring by profiling hepatic gene expression and lipid content.
Methods
Male Apc1638N mice (prone to intestinal tumor formation) were fed diets containing replete (control, CTRL), mildly deficient (DEF), or supplemental (SUPP) quantities of vitamins B2, B6, B12, and folate for 8 weeks before mating with control-fed wild type females. Wild type offspring were euthanized at weaning and hepatic gene expression profiled. Apc1638N offspring were fed a replete diet and euthanized at 28 weeks of age to assess tumor burden.
Results
No differences in intestinal tumor incidence or burden were found between male Apc1638N offspring of different paternal diet groups. Although in female Apc1638N offspring there were no differences in tumor incidence or multiplicity, a stepwise increase in tumor volume with increasing paternal B vitamin intake was observed. Interestingly, female offspring of SUPP and DEF fathers had a significantly lower body weight than those of CTRL fed fathers. Moreover, hepatic trigylcerides and cholesterol were elevated 3-fold in adult female offspring of SUPP fathers. Weanling offspring of the same fathers displayed altered expression of several key lipid-metabolism genes. Hundreds of differentially methylated regions were identified in the paternal sperm in response to DEF and SUPP diets. Aside from a few genes including Igf2, there was a striking lack of overlap between these genes differentially methylated in sperm and differentially expressed in offspring.
Conclusions
In this animal model, modulation of paternal B vitamin intake prior to mating alters offspring weight gain, lipid metabolism and tumor growth in a sex-specific fashion. These results highlight the need to better define how paternal nutrition affects the health of offspring.

背景
母体营养对子代健康与疾病风险的重要性已得到广泛证实。新兴研究证据表明，父代饮食同样可能对子代健康产生影响。
目的
本研究旨在明确：孕前父体B族维生素（B vitamin）摄入水平的调控，是否会改变子代的肠道肿瘤发生情况。此外，本研究还通过分析子代肝脏基因表达谱与脂质含量，试图阐明观察到的子代体重差异背后的潜在机制。
方法
雄性Apc1638N小鼠（易患肠道肿瘤）在与喂食标准饲料的野生型雌鼠交配前8周，分别喂食富含（对照组，CTRL）、轻度缺乏（DEF组）或补充（SUPP组）维生素B2、B6、B12与叶酸的饲料。野生型子代在断奶时实施安乐死，并进行肝脏基因表达谱分析。Apc1638N子代则喂食标准饲料，于28周龄时实施安乐死以评估肿瘤负荷。
结果
不同父代饮食组的雄性Apc1638N子代小鼠，其肠道肿瘤发生率与肿瘤负荷均无显著差异。尽管雌性Apc1638N子代的肿瘤发生率与肿瘤多发率无明显差异，但随着父代B族维生素摄入水平升高，子代肿瘤体积呈现逐步升高的趋势。值得注意的是，SUPP组与DEF组父代所产生的雌性子代，其体重均显著低于CTRL组父代的雌性子代。此外，SUPP组父代的成年雌性子代肝脏甘油三酯与胆固醇水平升高了3倍。相同父代的断奶子代，其体内若干关键脂质代谢相关基因的表达发生了改变。针对DEF组与SUPP组父代的精子分析，共鉴定出数百个差异甲基化区域（differentially methylated regions）。除胰岛素样生长因子2（Igf2）等少数基因外，父代精子中发生差异甲基化的基因与子代体内差异表达的基因之间，几乎不存在重叠。
结论
在本动物模型中，交配前调控父代B族维生素摄入水平，会以性别特异性的方式改变子代的体重增长、脂质代谢与肿瘤生长情况。本研究结果凸显了深入阐明父代营养如何影响子代健康的必要性。