The impact of thyroid hormone in seasonal breeding has a restricted transcriptional signature
Thyroid hormone (TH) directs seasonal breeding through reciprocal regulation of TH deiodinase (Dio2/Dio3) gene expression in tanycytes in the ependymal zone of the medio-basal hypothalamus (MBH). Thyrotropin secretion by the pars tuberalis (PT) is a major photoperiod-dependent upstream regulator of Dio2/Dio3 gene expression. Long days enhance thyrotropin production, which increases Dio2 expression and suppresses Dio3 expression, thereby heightening TH signaling in the MBH. Short days appear to exert the converse effect. Here, we combined endocrine profiling and transcriptomics to understand how photoperiod and TH control the ovine reproductive status through effects on hypothalamic function. Almost 3000 genes showed altered hypothalamic expression between the breeding- and non-breeding seasons, showing gene ontology enrichment for cell signaling, epigenetics and neural plasticity. In contrast, acute switching from a short (SP) to a long photoperiod (LP) affected the expression of a much smaller core of 134 LP-responsive genes, including a canonical group previously linked to photoperiodic synchronization. Reproductive switch-off at the end of the winter breeding season was completely blocked by thyroidectomy (THX), despite a very modest effect on the hypothalamic transcriptome. Only 49 genes displayed altered expression between intact and THX ewes, including less than 10% of the LP-induced gene set. Neuroanatomical mapping showed that many LP-induced genes were expressed in the PT, independently of the TH status. In contrast, TH-sensitive seasonal genes were principally expressed in the ependymal zone. These data highlight the distinctions between seasonal remodeling effects, which appear to be largely independent of TH, and TH-dependent localised effects which are permissive for transition to the non-breeding state.
KeywordsBiological rhythms Circannual clock GnRH Melatonin Pars tuberalis Photoperiod Pituitary Seasonality Sheep Tanycytes Thyrotropin
Differentially expressed genes
In situ hybridization
Pars distalis of the pituitary
Pars tuberalis of the pituitary
We thank the staff of the CIRE platform for assistance with surgical procedures, Damien Capo, Olivier Lasserre and Didier Dubreuil from the Unité Expérimentale PAO no. 1297 (EU0028) for taking care of the animals and blood sampling, staff of the IGF sequencing platform (Montpellier, France) and Shona Wood (Manchester University, UK) for help with bioinformatics.
This work was supported by a Career Integration Grant (No. 320553) from the FP7-Marie-Curie actions (H.D.).
DL, DC & HD carried out the molecular lab work; JC carried out surgeries; ED performed the RNAseq experiments; HD designed the study, performed data analysis and drafted the manuscript; DH contributed intellectual support and helped draft the manuscript. All authors gave final approval for publication.
Compliance with ethical standards
Conflict of interest
The authors have no conflict of interest.
All experimental procedures were performed in accordance with international (directive 2010/63/UE) and national legislation (décret no. 2013–118) governing the ethical use of animals in research (authorization no. E37–175-2 and no. A38 801). All procedures used in this work were evaluated by a local ethics committee (Comité d’Ethique en Expérimentation Animale Val de Loire) and approved by the Ministry of Higher Education and Research (Project No. 00710.02).
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