Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/128328
Type: Thesis
Title: Contribution of insulin-like growth factor system and growth hormone insulin-like growth factor 1 axis genes to heterosis in a bovine fetus model
Author: Javadmanesh, Ali
Issue Date: 2013
School/Discipline: School of Animal and Veterinary Sciences
Abstract: Heterosis, the superiority of hybrids over the average of purebred parents, has been used for centuries to obtain higher yields in animal production. Molecular mechanisms of heterosis remain poorly understood and traditional genetic models based on dominance and overdominance largely fail to explain heterosis. This thesis is based on a bovine (Bos taurus × Bos indicus) heterosis model with high levels of heterosis in birthweight and postnatal growth and development associated with increased plasma insulin-like growth factor 1 (IGF1) concentrations. We hypothesised that heterosis is programmed prenatally and orchestrated by the IGF system and the growth hormone (GH)-IGF1 axis, which are fundamental for pre- and postnatal growth and development. We further hypothesised that epigenetic mechanisms involved in control of IGFs, i.e. as miRNA interference and retrotransposon insertion, contribute to heterosis. The aims of this project were to study the contribution of IGF system and GH-IGF1 axis transcripts, and epigenetic regulatory elements, on fetal growth and development of purebred Angus and Brahman cattle and their reciprocal crosses. Quantitative real time-PCR was used to quantify transcript abundance of IGF1 overall transcript, IGF1 class 1 and class 2, IGF1R, insulin receptor (IR) overall transcript, IR-A, IR-B, GH, GHR overall transcript, GHR-1A, GHR-1B, GHR-1C, insulin-like growth factor binding protein 1 (IGFBP1), IGFBP2, IGFBP3, IGFBP4, IGFBP5, IGFBP6, IGFBP7 and IGFBP8, in brain, cotyledon, heart, kidney, liver, lung, skeletal muscle and testis of Day-48 embryos, Day-153 fetuses and 12-month old juveniles. A miRNA abundance profile of fetal liver was obtained using miRNA arrays. Genetic, fetal sex and heterosis effects on transcript abundances were estimated using general linear models. Lack of data on developmental-stage and tissue-specific expression required an initial comparative gene expression study across key developmental stages and tissues. IGF system and GH-IGF1 axis transcripts showed tissue-specific expression patterns that differed across developmental stages. There was no detectable GH mRNA in tissues studied. The abundance of most transcripts in juvenile tissue was lower than in fetal tissue, except in liver, which showed increased IGF1, GHR and IGFBP4 expression and no change for IR, IGFBP1, IGFBP3 and IGFBP6 transcript. Our data showed negative or no molecular heterosis for liver IGFBP transcripts. Reduced expression of these IGF-modulators suggested an increase in available IGF1 in the fetus. We found molecular heterosis in liver GHR, as the major GHR downstream pathways involve IGF1, we concluded that heterosis in liver IGF1 class 2 transcripts was a result of increased liver GHR-1A mRNA. Several miRNAs, predicted to target 3’ UTRs of IGF system genes and GHR, were differentially expressed in different genotypes and may have a regulatory role in transcription of IGF system and GHR genes in bovine fetal liver. However, more experiments with an increased sample size for miRNA profiling are required to assess this further. Among studied tissues, fetal liver appears to be the most important tissue to study the molecular mechanisms of heterosis. In conclusion, it was demonstrated that mRNA transcripts and miRNAs in the developmentally important IGF system, and GHR transcripts, contribute to molecular heterosis in the bovine model. We propose that liver GHR-1A - IGF1 class 2 transcripts are important factors in molecular heterosis which may contribute to the reported heterosis in birth weight. Furthermore, miRNAs that regulate IGF system/GHR transcripts may contribute to bovine molecular and phenotypic heterosis postnatally.
Advisor: Hiendleder, Stefan
Kind, Karen
Dissertation Note: Thesis (Ph.D.) -- University of Adelaide, School of Animal & Veterinary Sciences, 2014
Provenance: This electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at: http://www.adelaide.edu.au/legals
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