title: Tissue-specific and minor inter-individual variation in imprinting of IGF2R is a common feature of Bos taurus Concepti and not correlated with fetal weight.
abstract: 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 by in-vitro embryo culture. Imprinted maternal expression of murine Igf2r is well documented for all fetal tissues excluding brain, but polymorphic imprinting and biallelic expression were reported for IGF2R in 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 68 Bos taurus fetuses at Day 80 of gestation (28% term) and found predominantly maternal IGF2R expression 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 by in-vitro fertilization (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 of Bos taurus IGF2R is 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 in IGF2R expression in overgrown fetuses could be modulated through other mechanisms than changes in imprinting.
authors.affiliation: Chair for Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Bebbere
authors.forename: Stefan
authors.initials: S
authors.lastname: Bauersachs
authors.forename: Rainer W
authors.initials: RW
authors.lastname: Fürst
authors.forename: Horst-Dieter
authors.initials: HD
authors.lastname: Reichenbach
authors.forename: Myriam
authors.initials: M
authors.lastname: Reichenbach
authors.forename: Ivica
authors.initials: I
authors.lastname: Medugorac
authors.forename: Susanne E
authors.initials: SE
authors.lastname: Ulbrich
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
authors.forename: Sergio
authors.initials: S
authors.lastname: Ledda
authors.forename: Stefan
authors.initials: S
authors.lastname: Hiendleder
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002417:Cattle / Q000196:embryology* / Q000235:genetics*; D005260:Female; D005307:Fertilization in Vitro; D020567:Fetal Weight / Q000235:genetics; D005333:Fetus / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D017527:Receptor, IGF Type 2 / Q000235:genetics*; D013045:Species Specificity
chemical_list: D017527:Receptor, IGF Type 2