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

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.

Thyroid hormone links environmental signals to DNA methylation

“…Additionally, grooming of mouse pups by mothers increased DNMT3a mRNA levels in the hippocampus of pups. These changes in mRNA levels were accompanied by an association between circulating T3 levels and DNMT3a abundance, and increased TR binding by T3 led to increased DNA methylation at the oxytocin promoter [64]. Together, these data indicate that DNMT3 transcription and DNA methylation patterns can be regulated by T3 and TR binding to TRE in diverse groups of vertebrates and in different contexts.…”