饮食诱导的父源性肥胖通过介导精子表观遗传修饰损害子代认知功能。
Diet-Induced Paternal Obesity Impairs Cognitive Function in Offspring by Mediating Epigenetic Modifications in Spermatozoa.
机构信息
Key Laboratory of Reproductive Genetics, Ministry of Education, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Center for Reproductive Medicine, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
出版信息
Obesity (Silver Spring). 2018 Nov;26(11):1749-1757. doi: 10.1002/oby.22322.
OBJECTIVE
This study aimed to determine the effects of diet-induced paternal obesity on cognitive function in mice offspring.
METHODS
Male mice (F0) were randomized to receive either a control diet (10 kcal% fat) or a high-fat diet (HFD; 60 kcal% fat) for 10 weeks before being mated with normal females to generate F1 offspring. Male F1 offspring were mated with normal females to generate F2 offspring. Behavioral tests were used to assess cognitive functions in F1 and F2 offspring. Reduced representation bisulfite sequencing was used to the explore mechanisms of epigenetic inheritance.
RESULTS
HFD-induced paternal obesity resulted in cognitive impairments in F1 offspring, potentially due, at least in part, to increased methylation of the BDNF gene promoter, which was inherited from F0 spermatozoa. BDNF/tyrosine receptor kinase B signaling was associated with cognitive impairments in HFD-fed F1 offspring. However, there were no significant changes in F2 offspring.
CONCLUSIONS
The findings provide evidence of intergenerational effects of paternal obesity on cognitive function in offspring occurring via epigenetic spermatozoan modifications.
目的
本研究旨在确定饮食诱导的父系肥胖对小鼠后代认知功能的影响。
方法
雄性小鼠（F0）在与正常雌性交配产生 F1 后代之前，随机分为接受对照饮食（10%卡路里脂肪）或高脂肪饮食（HFD；60%卡路里脂肪）10 周。雄性 F1 后代与正常雌性交配产生 F2 后代。行为测试用于评估 F1 和 F2 后代的认知功能。简化重亚硫酸盐测序用于探索表观遗传遗传的机制。
结果
HFD 诱导的父系肥胖导致 F1 后代认知功能障碍，这可能至少部分归因于 BDNF 基因启动子的甲基化增加，这种增加来自 F0 精子。BDNF/酪氨酸受体激酶 B 信号与 HFD 喂养的 F1 后代的认知障碍有关。然而，F2 后代没有发生显著变化。
结论
这些发现提供了证据表明，父系肥胖通过精子表观遗传修饰对后代的认知功能产生了代际影响。
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