Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort.
Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort.
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DOI：
10.1186/1741-7015-11-29
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发表时间：
2013-02-06
期刊：
影响因子：
9.3
通讯作者：
Hoyo C
中科院分区：
文献类型：
--
作者：
Soubry A;Schildkraut JM;Murtha A;Wang F;Huang Z;Bernal A;Kurtzberg J;Jirtle RL;Murphy SK;Hoyo C
流行病学和动物模型研究的数据表明，孕期营养可能会影响后代的健康状况。这些跨代效应现在正被表观遗传机制水平上的破坏所解释。除了体外环境暴露外，在更早的时间点，如精子发生或卵子发生期间，对印记基因甲基化特征重新编程的可能影响以前还没有被考虑过。在这项研究中，我们的目的是确定先兆性肥胖与后代DNA甲基化之间的关系，特别是印记的胰岛素样生长因子2(IGF2)基因的差异甲基化区域(DMRS)。我们检测了79名新生儿的脐血白细胞DNA，这些新生儿出生于2005年7月至2006年11月，在北卡罗来纳州达勒姆的杜克大学医院出生。他们的母亲在怀孕期间参加了新生儿表观遗传学研究(Nest)。父母特征通过标准化问卷调查和病历记录获得。用亚硫酸氢盐焦磷酸测序分析两个DMR的DNA甲基化模式，一个在IGF2的上游(IGF2 DMR)，一个在邻近的H19基因的上游(H19 DMR)。多元回归模型被用来确定后代的DNA甲基化模式与受孕前父母肥胖之间的潜在联系。肥胖定义为体重指数≥为30 kg/m2。IGF2DMR的低甲基化与父亲肥胖有关。即使在调整了母亲和新生儿的几个特征后，我们也观察到后代的DNA甲基化与父亲肥胖之间持续的负相关(β系数为-5.28，P=0.003)。在H19DMR中，未检测到甲基化模式与父亲肥胖之间的显著关联。我们的数据表明，肥胖母亲所生的新生儿中IGF2和H19 DMR的DNA甲基化增加，但有必要进行更大规模的研究，以进一步探索母亲肥胖或生活方式对后代表观基因组的潜在影响。虽然我们的小样本数量有限，但我们的数据表明，在精子发生期间，父亲肥胖对印记标记重新编程的先入为主的影响。鉴于印记保真度在生物学上的重要性，我们的研究为父亲肥胖的跨代效应提供了证据，这可能会影响后代未来的健康状况。
Data from epidemiological and animal model studies suggest that nutrition during pregnancy may affect the health status of subsequent generations. These transgenerational effects are now being explained by disruptions at the level of the epigenetic machinery. Besides in vitro environmental exposures, the possible impact on the reprogramming of methylation profiles at imprinted genes at a much earlier time point, such as during spermatogenesis or oogenesis, has not previously been considered. In this study, our aim was to determine associations between preconceptional obesity and DNA methylation profiles in the offspring, particularly at the differentially methylated regions (DMRs) of the imprinted Insulin-like Growth Factor 2 (IGF2) gene. We examined DNA from umbilical cord blood leukocytes from 79 newborns, born between July 2005 and November 2006 at Duke University Hospital, Durham, NC. Their mothers participated in the Newborn Epigenetics Study (NEST) during pregnancy. Parental characteristics were obtained via standardized questionnaires and medical records. DNA methylation patterns at two DMRs were analyzed by bisulfite pyrosequencing; one DMR upstream of IGF2 (IGF2 DMR), and one DMR upstream of the neighboring H19 gene (H19 DMR). Multiple regression models were used to determine potential associations between the offspring's DNA methylation patterns and parental obesity before conception. Obesity was defined as body mass index (BMI) ≥30 kg/m2. Hypomethylation at the IGF2 DMR was associated with paternal obesity. Even after adjusting for several maternal and newborn characteristics, we observed a persistent inverse association between DNA methylation in the offspring and paternal obesity (β-coefficient was -5.28, P = 0.003). At the H19 DMR, no significant associations were detected between methylation patterns and paternal obesity. Our data suggest an increase in DNA methylation at the IGF2 and H19 DMRs among newborns from obese mothers, but a larger study is warranted to further explore the potential effects of maternal obesity or lifestyle on the offspring's epigenome. While our small sample size is limited, our data indicate a preconceptional impact of paternal obesity on the reprogramming of imprint marks during spermatogenesis. Given the biological importance of imprinting fidelity, our study provides evidence for transgenerational effects of paternal obesity that may influence the offspring's future health status.
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影响因子：
30.8
作者：
Gicquel, C;Rossignol, S;Le Bouc, Y
通讯作者：
Le Bouc, Y
影响因子：
64.5
作者：
Carone BR;Fauquier L;Habib N;Shea JM;Hart CE;Li R;Bock C;Li C;Gu H;Zamore PD;Meissner A;Weng Z;Hofmann HA;Friedman N;Rando OJ
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14.9
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Huang, ZQ;Wen, YQ;Murphy, SK
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64.5
作者：
BAKER, J;LIU, JP;EFSTRATIADIS, A
通讯作者：
EFSTRATIADIS, A
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56.9
作者：
Cui, HM;Cruz-Correa, M;Feinberg, AP
通讯作者：
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