Immunisation of the somatostatin gene alters hypothalamic-pituitary-liver gene expressions and enhances growth in Dazu black goats

다국어 초록 (Multilingual Abstract)

Objective: Somatostatin (SS) plays important regulatory roles in animal growth and reproduction by affecting the synthesis and secretion of growth hormone (GH). However, the mechanism by which SS regulates growth and development in goats is still unclear.Methods: In this study, we randomly selected eight 7-month-old Dazu black goats (DBGs) of similar body weight and equally assigned four bucks as the immunised and negative control groups. The immunised group received the Salmonella typhi attenuated vaccine <i>X9241</i> (ptCS/2SS-asd) orally, whilst the negative control group received the empty vector vaccine <i>X9241</i> (pVAX-asd) orally.Results: The SS concentration in the serum of goats in the immunised group was significantly lower than that in the negative control group, and the daily gain was significantly higher (p<0.05). SS-14 DNA vaccine immunisation resulted in significantly higher concentrations of growth-related hormones such as GH-releasing hormone and insulin growth factor 1 (IGF-1) in the serum of goats (p<0.05). RNA-seq analysis of hypothalamus of oral SS-14 DNA vaccine and negative control DBGs identified 31 differentially expressed genes (DEGs). Pituitary gland identified 164 DEGs. A total of 246 DEGs were detected in the liver by RNA-seq. Gene ontology of DEGs was enriched in mitochondrial envelope, extracellular region, receptor binding and cell proliferation. The biological metabolic pathways associated with DEGs were explored by Kyoto encyclopedia of genes and genomes analysis. DEGs were associated with metabolic pathways, oxidative phosphorylation, vitamin digestion and absorption and galactose metabolism. These candidate genes (e.g. <i>DGKK</i>, <i>CYTB</i>, <i>DUSP1</i>, and <i>LRAT</i>) may provide references for exploring the molecular mechanisms by which SS promotes growth and development.Conclusion: Overall, these results demonstrated that the SS DNA vaccine enhanced the growth of DBGs by altering growth-related hormone concentrations and regulating the expression of growth-related genes in the hypothalamic–pituitary–liver axis.

다국어 초록 (Multilingual Abstract)

Objective: Somatostatin (SS) plays important regulatory roles in animal growth and reproduction by affecting the synthesis and secretion of growth hormone (GH). However, the mechanism by which SS regulates growth and development in goats is still unclear.
Methods: In this study, we randomly selected eight 7-month-old Dazu black goats (DBGs) of similar body weight and equally assigned four bucks as the immunised and negative control groups. The immunised group received the Salmonella typhi attenuated vaccine X9241 (ptCS/2SS-asd) orally, whilst the negative control group received the empty vector vaccine X9241 (pVAX-asd) orally.
Results: The SS concentration in the serum of goats in the immunised group was significantly lower than that in the negative control group, and the daily gain was significantly higher (p<0.05). SS-14 DNA vaccine immunisation resulted in significantly higher concentrations of growth-related hormones such as GH-releasing hormone and insulin growth factor 1 (IGF-1) in the serum of goats (p<0.05). RNA-seq analysis of hypothalamus of oral SS-14 DNA vaccine and negative control DBGs identified 31 differentially expressed genes (DEGs). Pituitary gland identified 164 DEGs. A total of 246 DEGs were detected in the liver by RNA-seq. Gene ontology of DEGs was enriched in mitochondrial envelope, extracellular region, receptor binding and cell proliferation. The biological metabolic pathways associated with DEGs were explored by Kyoto encyclopedia of genes and genomes analysis. DEGs were associated with metabolic pathways, oxidative phosphorylation, vitamin digestion and absorption and galactose metabolism. These candidate genes (e.g. DGKK, CYTB, DUSP1, and LRAT) may provide references for exploring the molecular mechanisms by which SS promotes growth and development.
Conclusion: Overall, these results demonstrated that the SS DNA vaccine enhanced the growth of DBGs by altering growth-related hormone concentrations and regulating the expression of growth-related genes in the hypothalamic–pituitary–liver axis.

참고문헌 (Reference)

• 1 Chen SF, "fastp : an ultra-fast all-in-one FASTQ preprocessor" 34 : i884-i890, 2018
• 2 Pertea M, "Transcript level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown" 11 : 1650-1667, 2016
• 3 Dawson JM, "The effect of immunization against somatostatin and beta-agonist administration alone and in combination on growth and carcass composition in young steers" 64 : 37-51, 1997
• 4 Chen JX, "The association analysis between Cytb polymorphism and growth traits in three Chinese donkey breeds" 126 : 306-309, 2009
• 5 Manina AA, "Subcellular changes in posterior hypothalamus at the peak of immune response" 11 : 51-53, 1980
• 6 Na R, "SNP screening of the MSTN gene and correlation analysis between genetic polymorphisms and growth traits in Dazu black goat" 32 : 558-565, 2021
• 7 Vicennati V, "Response of the hypothalamic-pituitary-adrenocortical axis to high-protein/fat and high-carbohydrate meals in women with different obesity phenotypes" 87 : 3984-3988, 2002
• 8 Zhao Z, "Reproductive characteristics of Dazu black goats, a newly discovered Chinese indigenous breed resource with high litter sizes" 51 : 399-403, 2019
• 9 Li B, "RSEM : accurate transcript quantification from RNA-Seq data with or without a reference genome" 12 : 23-, 2011
• 10 Hu Y, "Profiles of mRNA expression of related genes in the duck hypothalamus-pituitary growth axis during embryonic and early post-hatch development" 559 : 38-43, 2015
• 11 Han Y, "Potent effect of KISS1-54 DNA vaccine compared with KISS1-10 DNA vaccine in inhibiting the fertility of female rats" 36 : 6631-6639, 2018
• 12 Granata R, "Peripheral activities of growth hormone-releasing hormone" 39 : 721-727, 2016
• 13 Han YG, "Oral SS-14 DNA vaccine is more potent than Oral SS-28 DNA vaccine in promoting rat lactation" 51 : 1711-1719, 2019
• 14 Wójcik-Gladysz A, "Obestatin stimulates the somatotrophic axis activity in sheep" 1678 : 278-287, 2018
• 15 Goshu HA, "Novel copy number variations of the CHRM3 gene associated with gene expression and growth traits in Chinese Datong yak(Bos grunniens)" 48 : 156-165, 2020
• 16 Love MI, "Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2" 15 : 550-, 2014
• 17 Liang C, "Mitochondrial microproteins link metabolic cues to respiratory chain biogenesis" 40 : 111204-, 2022
• 18 Romanò N, "Median eminence blood flow influences food intake by regulating ghrelin access to the metabolic brain" 8 : e165763-, 2023
• 19 Frapin M, "Maternal protein restriction in rats alters the expression of genes involved in mitochondrial metabolism and epitranscriptomics in fetal hypothalamus" 12 : 1464-, 2020
• 20 Ravichandran M, "Live, genetically attenuated, cold-chain-free cholera vaccine-a research and development journey : light at the end of a long tunnel" 29 : 1-7, 2022
• 21 Purwana IN, "Induction of dual specificity phosphatase 1(DUSP1)by gonadotropin-releasing hormone(GnRH)and the role for gonadotropin subunit gene expression in mouse pituitary gonadotroph LbetaT2 cells" 82 : 352-362, 2010
• 22 Prickett AR, "Imprinted gene expression and function of the dopa decarboxylase gene in the developing heart" 9 : 676543-, 2021
• 23 Mizusawa N, "Identification of protease serine S1 family member 53 as a mitochondrial protein in murine islet beta cells" 14 : 1-13, 2022
• 24 Irizarry VTC, "Hypothalamic estrogen signaling and adipose tissue metabolism in energy homeostasis" 13 : 898139-, 2022
• 25 Nagatsuma K, "Hepatic stellate cells that coexpress LRAT and CRBP-1 partially contribute to portal fibrogenesis in patients with human viral hepatitis" 34 : 243-252, 2014
• 26 Kim D, "HISAT : a fast spliced aligner with low memory requirements" 12 : 357-360, 2015
• 27 Seoane LM, "Growth hormone and somatostatin directly inhibit gastric ghrelin secretion. an in vitro organ culture system" 30 : RC22-RC25, 2007
• 28 Gardiner J, "Ghrelin gets its goat" 7 : 193-194, 2008
• 29 Birzniece V, "Gender difference in the neuroendocrine regulation of growth hormone axis by selective estrogen receptor modulators" 97 : E521-E527, 2012
• 30 Liu Z, "Follicle-stimulating hormone(FSH)promotes retinol uptake and metabolism in the mouse ovary" 16 : 52-, 2018
• 31 Uddin A, "Factors influencing codon usage of mitochondrial ND1 gene in pisces, aves and mammals" 37 : 17-26, 2017
• 32 Chaves FM, "Effects of the isolated and combined ablation of growth hormone and IGF-1 receptors in somatostatin neurons" 163 : bqac045-, 2022
• 33 Cossin-Sevrin N, "Effect of prenatal glucocorticoids and thyroid hormones on developmental plasticity of mitochondrial aerobic metabolism, growth and survival: an experimental test in wild great tits" 225 : jeb243414-, 2022
• 34 Han Y, "Effect of a novel somatostatin-14DNA vaccine fused to tPA signal peptide and CpG adjuvant on goat lactation and milk composition" 187 : 106107-, 2020
• 35 Vázquez-Borrego MC, "Direct and systemic actions of growth hormone receptor(GHR)-signaling on hepatic glycolysis, de novo lipogenesis and insulin sensitivity, associated with steatosis" 144 : 155589-, 2023
• 36 Wasinski F, "Central growth hormone action regulates neuroglial and proinflammatory markers in the hypothalamus of male mice" 806 : 137236-, 2023
• 37 Han YG, "A nonsynonymous SNP within the AMH gene is associated with litter size in Dazu black goats" 33 : 992-996, 2022
• 38 Mosquera L, "A mRNA localized to the vegetal cortex of Xenopus oocytes encodes a protein with a nanos-like zinc finger domain" 117 : 377-386, 1993