Tissue-specific and minor inter-individual variation in imprinting ofIGF2Ris a common feature ofBos taurusconcepti and not correlated with fetal weight

The insulin-like growth factor 2 receptor (IGF2R) is essential for prenatal growth regulation and shows gene dosage effects on fetal weight that can be affected byin-vitroembryo culture. Imprinted maternal expression of murineIgf2ris well documented for all fetal tissues excluding brain, but polymorphic imprinting and biallelic expression were reported forIGF2Rin human. These differences have been attributed to evolutionary changes correlated with specific reproductive strategies. However, data from species suitable for testing this hypothesis are lacking. The domestic cow (Bos taurus) carries a single conceptus with a similar gestation length as human. We identified 12 heterozygous concepti informative for imprinting studies among 68Bos taurusfetuses at Day 80 of gestation (28% term) and found predominantly maternalIGF2Rexpression in all fetal tissues but brain, which escapes imprinting. Inter-individual variation in allelic expression bias,i.e. expression of the repressed paternal allele relative to the maternal allele, ranged from 4.6−8.9% in heart, 4.3−10.2% in kidney, 6.1−11.2% in liver, 4.6−15.8% in lung and 3.2−12.2% in skeletal muscle. Allelic bias for mesodermal tissues (heart, skeletal muscle) differed significantly (P<0.05) from endodermal tissues (liver, lung). The placenta showed partial imprinting with allelic bias of 22.9−34.7% and differed significantly (P<0.001) from all other tissues. Four informative fetuses were generated byin-vitrofertilization (IVF) with embryo culture and two individuals displayed fetal overgrowth. However, there was no evidence for changes in imprinting or DNA methylation after IVF, or correlations between allelic bias and fetal weight. In conclusion, imprinting ofBos taurusIGF2Ris similar to mouse except in placenta, which could indicate an effect of reproductive strategy. Common minor inter-individual variation in allelic bias and absence of imprinting abnormalities in IVF fetuses suggest changes inIGF2Rexpression in overgrown fetuses could be modulated through other mechanisms than changes in imprinting.