A high plane of nutrition during early life alters the hypothalamic transcriptome of heifer calves

José M Sánchez,Colin J Byrne,Alan K Kelly,Kate Keogh,Pat Lonergan,David A Kenny

doi:10.1038/s41598-021-93080-4

Abstract

The aim was to examine the effect of rapid body weight gain during early calfhood consistent with earlier sexual development on the transcriptional profile of the hypothalamus. Angus X Holstein–Friesian heifer calves (19 ± 5 days of age) were offered a high (HI, n = 14) or moderate (MOD, n = 15) plane of nutrition from 3 to 21 weeks of age to achieve a growth rate of 1.2 kg/d and 0.5 kg/d, respectively. Following euthanasia at 21 weeks, the arcuate nucleus (ARC) region was separated from the remainder of the hypothalamus and both were subjected to RNA-Seq. HI calves exhibited altered expression of 80 and 39 transcripts in the ARC and the remaining hypothalamus, respectively (P < 0.05) including downregulation of AGRP and NPY and upregulation of POMC, previously implicated in precocious sexual development. Stress-signaling pathways were amongst the most highly dysregulated. Organ morphology, reproductive system development and function, and developmental disorder were amongst the networks derived from differentially expressed genes (DEGs) in the ARC. Gene co-expression analysis revealed DEGs within the ARC (POMC, CBLN2, CHGA) and hypothalamus (PENK) as hub genes. In conclusion, enhanced nutrition during early calfhood alters the biochemical regulation of the hypothalamus consistent with advanced sexual development in the prepubertal heifer.

Highlights

The aim was to examine the effect of rapid body weight gain during early calfhood consistent with earlier sexual development on the transcriptional profile of the hypothalamus
Another population of hypothalamic kisspeptin neurons is localized in the preoptic area (POA) in ruminants and evidence suggests that they play a pivotal role in mediating positive feedback action of oestrogen to induce the gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) surge
Recent advances in deep-sequencing technology (RNA-Seq) data derived from the current study have been deposited within NCBI’s Gene Expression Omnibus and are available through IDs GSE153495 and GSE153498 for hypothalamus and arcuate nucleus datasets, respectively

Summary

Introduction

The aim was to examine the effect of rapid body weight gain during early calfhood consistent with earlier sexual development on the transcriptional profile of the hypothalamus. Signals from hormones associated with metabolic status such as leptin, ghrelin, insulin and insulin-like growth factor 1 (IGF-1) are integrated in the ARC through intermediate neuronal (kisspeptin neurons) and glial circuits that regulate gonadotropin-releasing hormone (GnRH) pulse generation (reviewed by Cardoso et al.[13]). Another population of hypothalamic kisspeptin neurons is localized in the preoptic area (POA) in ruminants and evidence suggests that they play a pivotal role in mediating positive feedback action of oestrogen to induce the GnRH/luteinizing hormone (LH) surge (reviewed by Uenoyama et al.[14]). Age at puberty onset is inversely related to plane of nutrition and metabolic status, but this relationship is apparently more potent the earlier in life dietary augmentation is implemented[10]

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