Keogh Kate, Coen Stephen, Lonergan Pat, Fair Sean, Kenny David A
Teagasc Animal and Grassland Research and Innovation Centre, Grange, Dunsany, Co. Meath, Ireland.
School of Agriculture and Food Science, University College Dublin, Belfield, Dublin 4, Ireland.
BMC Genomics. 2025 May 9;26(1):466. doi: 10.1186/s12864-025-11656-0.
Reproductive development may be advanced in bull calves through enhanced dietary intake during the early life period. This effect between enhanced nutrition with subsequent earlier reproductive development is orchestrated through signalling within the hypothalamic-pituitary-testicular axis. Within the hypothalamus, the arcuate nucleus (ARC) is crucial for the integration of peripheral metabolic status with subsequent gonadotropin releasing hormone (GnRH) signalling; however, the precise molecular control regulating this effect is not fully known. The aim of this study was to evaluate the global transcriptomic and proteomic responses to varied plane of nutrition during early calf-hood in young dairy bull calves. Additionally, we sought to integrate these 'omics' datasets to determine key genes and proteins contributing to earlier reproductive development. Between 2-12 weeks of age, 30 Holstein-Friesian bull calves (mean age: 17.5 days; mean bodyweight 48.8 kg), were offered either a high or moderate plane of nutrition with 15 calves in each group. At 12 weeks of age, all calves were euthanised and the ARC tissue isolated from each calf. The ARC tissue was then used for global transcriptomic (miRNAseq and mRNAseq) and proteomic analyses.
Bioinformatic analyses were undertaken to determine differentially expressed transcripts (FDR < 0.1; fold change > 1.5) between the dietary treatment groups, resulting in the identification of 1 differentially expressed miRNA (miR-2419-3p) and 83 differentially expressed mRNA in the ARC region. mRNA target gene prediction identified Complement 3 (C3) as a target of miR-2419-3p, suggesting a relationship between the two transcripts. Furthermore, through a co-regulatory network analysis conducted on the proteomics dataset, C3 was revealed as a hub protein. Additionally, through the proteomic network analysis, C3 was interacting with proteins involved in both insulin and GnRH signalling, highlighting a potential role for C3 in mediated the effect of enhanced nutritional status with earlier reproductive development within the ARC.
This study highlights an effect of altered plane of nutrition in early life on the molecular control of the hypothalamic ARC. Additionally, results generated suggest a potential role for the C3 gene in mediating the interaction between enhanced metabolic status with reproductive development within the ARC, regulated by miR-2419-3p.
通过在犊牛早期提高日粮摄入量，可能会促进公牛犊的生殖发育。营养增强与随后更早的生殖发育之间的这种效应是通过下丘脑 - 垂体 - 睾丸轴内的信号传导来协调的。在下丘脑中，弓状核（ARC）对于整合外周代谢状态与随后的促性腺激素释放激素（GnRH）信号传导至关重要；然而，调节这种效应的确切分子机制尚不完全清楚。本研究的目的是评估幼年奶牛公牛犊在犊牛早期不同营养水平下的整体转录组和蛋白质组反应。此外，我们试图整合这些“组学”数据集，以确定有助于早期生殖发育的关键基因和蛋白质。在2至12周龄期间，将30头荷斯坦 - 弗里生公牛犊（平均年龄：17.5天；平均体重48.8千克）分为两组，每组15头，分别给予高营养水平或中等营养水平的日粮。在12周龄时，对所有犊牛实施安乐死，并从每头犊牛分离出ARC组织。然后将ARC组织用于整体转录组（miRNAseq和mRNAseq）和蛋白质组分析。
进行生物信息学分析以确定日粮处理组之间差异表达的转录本（FDR < 0.1；变化倍数> 1.5），结果在ARC区域鉴定出1个差异表达的miRNA（miR - 2419 - 3p）和83个差异表达的mRNA。mRNA靶基因预测确定补体3（C3）是miR - 2419 - 3p的靶标，表明这两个转录本之间存在关联。此外，通过对蛋白质组数据集进行共调控网络分析，发现C3是一个枢纽蛋白。另外，通过蛋白质组网络分析，C3与参与胰岛素和GnRH信号传导的蛋白质相互作用，突出了C3在介导ARC内营养状况增强与早期生殖发育之间的效应中的潜在作用。
本研究强调了生命早期营养水平改变对下丘脑ARC分子调控的影响。此外，研究结果表明C3基因在介导ARC内代谢状态增强与生殖发育之间的相互作用中具有潜在作用，这种作用受miR - 2419 - 3p调控。
