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早期生活中温度暴露的变化会影响雌性幼鼠室旁核的表观遗传调控。

Early life variations in temperature exposure affect the epigenetic regulation of the paraventricular nucleus in female rat pups.

机构信息

Department of Biological Sciences, University of Toronto, Scarborough Campus, SW548, 1265 Military Trail, Scarborough, Toronto, Ontario, Canada M1C 1A4.

Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada.

出版信息

Proc Biol Sci. 2020 Oct 28;287(1937):20201991. doi: 10.1098/rspb.2020.1991.

Abstract

Early life maternal care received has a profound effect on later-life behaviour in adult offspring, and previous studies have suggested epigenetic mechanisms are involved. Changes in thyroid hormone receptor signalling may be related to differences in maternal care received and DNA methylation modifications. We investigated the effects of variations in temperature exposure (a proxy of maternal contact) and licking-like tactile stimulation on these processes in week-old female rat pups. We assessed thyroid hormone receptor signalling by measuring circulating triiodothyronine and transcript abundance of thyroid hormone receptors and the thyroid hormone-responsive genes DNA methyltransferase 3a and oxytocin in the paraventricular nucleus of the hypothalamus. DNA methylation of the oxytocin promoter was assessed in relation to changes in thyroid hormone receptor binding. Repeated room temperature exposure was associated with a decrease in thyroid hormone receptor signalling measures relative to nest temperature exposure, while acute room temperature exposure was associated with an increase. Repeated room temperature exposure also increased thyroid hormone receptor binding and DNA methylation at the oxytocin promoter. These findings suggest that repeated room temperature exposure may affect DNA methylation levels as a consequence of alterations in thyroid hormone receptor signalling.

摘要

早期的母婴护理对成年后代的后期行为有深远的影响,先前的研究表明,表观遗传机制也参与其中。甲状腺激素受体信号的变化可能与母婴护理和 DNA 甲基化修饰的差异有关。我们研究了温度暴露(母婴接触的代表)和类似舔舐的触觉刺激对这些过程的影响,这些过程发生在一周大的雌性幼鼠身上。我们通过测量下丘脑室旁核中循环三碘甲状腺原氨酸和甲状腺激素受体以及甲状腺激素反应基因 DNA 甲基转移酶 3a 和催产素的转录丰度来评估甲状腺激素受体信号。我们还评估了催产素启动子的 DNA 甲基化与甲状腺激素受体结合的变化之间的关系。与巢温暴露相比,反复室温暴露与甲状腺激素受体信号测量值的降低有关,而急性室温暴露与增加有关。反复室温暴露还增加了催产素启动子处的甲状腺激素受体结合和 DNA 甲基化。这些发现表明,反复的室温暴露可能会影响 DNA 甲基化水平,从而改变甲状腺激素受体信号。

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