Widespread Differential Maternal and Paternal Genome Effects on Fetal Bone Phenotype at Mid‐Gestation

Widespread Differential Maternal and Paternal Genome Effects on Fetal Bone Phenotype at Mid‐Gestation

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 quant...

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Published in:Journal of bone and mineral research Vol. 29; no. 11; pp. 2392 - 2404
Main Authors: Xiang, Ruidong, Lee, Alice MC, Eindorf, Tanja, Javadmanesh, Ali, Ghanipoor‐Samami, Mani, Gugger, Madeleine, Fitzsimmons, Carolyn J, Kruk, Zbigniew A, Pitchford, Wayne S, Leviton, Alison J, Thomsen, Dana A, Beckman, Ian, Anderson, Gail I, Burns, Brian M, Rutley, David L, Xian, Cory J, Hiendleder, Stefan
Format: Journal Article
Language:English
Published: United States Wiley Subscription Services, Inc 01-11-2014
Subjects:
Animals
Cattle
EPIGENETICS
Female
Fetus
Gene Expression Regulation, Developmental - physiology
GENETIC ANIMAL MODELS
Genome - physiology
Genomic Imprinting - physiology
Growth Plate - embryology
Male
Osteogenesis - physiology
Phenotype
Pregnancy
STATISTICAL METHODS
STATISTICAL METHODS
EPIGENETICS
GENETIC ANIMAL MODELS
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Summary: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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ISSN:0884-0431
1523-4681
DOI:10.1002/jbmr.2263