Widespread Differential Maternal and Paternal Genome Effects on Fetal Bone Phenotype at Mid‐Gestation |
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| Authors: | Ruidong Xiang Alice MC Lee Tanja Eindorf Ali Javadmanesh Mani Ghanipoor‐Samami Madeleine Gugger Carolyn J Fitzsimmons Zbigniew A Kruk Wayne S Pitchford Alison J Leviton Dana A Thomsen Ian Beckman Gail I Anderson Brian M Burns David L Rutley Cory J Xian Stefan Hiendleder |
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| Institution: | 1. Robinson Research Institute, The University of Adelaide, Adelaide, Australia;2. JS Davies Epigenetics and Genetics Group, School of Animal and Veterinary Sciences, Roseworthy Campus, The University of Adelaide, Adelaide, Australia;3. Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia;4. School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, Australia;5. Veterinary Health Centre, School of Animal and Veterinary Sciences, Roseworthy Campus, The University of Adelaide, Adelaide, Australia;6. The University of Queensland, Centre for Animal Science, Queensland Alliance for Food Innovation, Rockhampton, Queensland, Australia |
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| Abstract: | Parent‐of‐origin–dependent (epi)genetic factors are important determinants of prenatal development that program adult phenotype. However, data on magnitude and specificity of maternal and paternal genome effects on fetal bone are lacking. We used an outbred bovine model to dissect and quantify effects of parental genomes, fetal sex, and nongenetic maternal effects on the fetal skeleton and analyzed phenotypic and molecular relationships between fetal muscle and bone. Analysis of 51 bone morphometric and weight parameters from 72 fetuses recovered at day 153 gestation (54% term) identified six principal components (PC1–6) that explained 80% of the variation in skeletal parameters. Parental genomes accounted for most of the variation in bone wet weight (PC1, 72.1%), limb ossification (PC2, 99.8%), flat bone size (PC4, 99.7%), and axial skeletal growth (PC5, 96.9%). Limb length showed lesser effects of parental genomes (PC3, 40.8%) and a significant nongenetic maternal effect (gestational weight gain, 29%). Fetal sex affected bone wet weight (PC1, p < 0.0001) and limb length (PC3, p < 0.05). Partitioning of variation explained by parental genomes revealed strong maternal genome effects on bone wet weight (74.1%, p < 0.0001) and axial skeletal growth (93.5%, p < 0.001), whereas paternal genome controlled limb ossification (95.1%, p < 0.0001). Histomorphometric data revealed strong maternal genome effects on growth plate height (98.6%, p < 0.0001) and trabecular thickness (85.5%, p < 0.0001) in distal femur. Parental genome effects on fetal bone were mirrored by maternal genome effects on fetal serum 25‐hydroxyvitamin D (96.9%, p < 0.001) and paternal genome effects on alkaline phosphatase (90.0%, p < 0.001) and their correlations with maternally controlled bone wet weight and paternally controlled limb ossification, respectively. Bone wet weight and flat bone size correlated positively with muscle weight (r = 0.84 and 0.77, p < 0.0001) and negatively with muscle H19 expression (r = –0.34 and –0.31, p < 0.01). Because imprinted maternally expressed H19 regulates growth factors by miRNA interference, this suggests muscle‐bone interaction via epigenetic factors. © 2014 American Society for Bone and Mineral Research. |
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| Keywords: | GENETIC ANIMAL MODELS EPIGENETICS STATISTICAL METHODS |
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