
%0 Journal Article
%A Bebbere, D. 
%A Ulbrich, S. E. 
%A Zakhartchenko, V. 
%A Weppert, M. 
%A Reichenbach, H.-D. 
%A Meyer, H. H. D. 
%A Ledda, S. 
%A Wolf, E. 
%A Hiendleder, S. 
%T 261 PHENOTYPIC CHARACTERISTICS AND TISSUE-SPECIFIC <i>IGF2R/IGF2</i> EXPRESSION PARTITION BOVINE FETAL OVERGROWTH ASSOCIATED WITH <i>IN VITRO</i> FERTILIZATION AND SOMATIC CELL NUCLEAR TRANSFER CLONING
%J Reproduction, Fertility and Development
%D 2006/12/12
%V 19
%N 1
%P 247-247
%K 
%R https://doi.org/10.1071/RDV19N1AB261
%U https://www.publish.csiro.au/paper/RDV19N1AB261 
%X Large offspring syndrome (LOS) in ruminants refers to various poorly defined organ pathologies that are associated with fetal overgrowth and are encountered after a range of embryo manipulations (Rhind et al. 2003 Nat. Rev. Genet. 4, 855&#8211;864). We have explored the effects of somatic cell nuclear transfer (NT) and in vitro fertilization (IVF) on phenotype and relative expression levels of 2 imprinted genes important for fetal growth, insulin-like growth factor 2 (IGF2) and its receptor (IGF2R). Viable bovine fetuses were recovered near the end of the first trimester of pregnancy, and skeletal muscle, liver, and lung were sampled for real-time RT-PCR analyses. We compared NT-fetuses (n = 23), IVF-fetuses (n = 24), and fetuses generated by artificial insemination (controls, n = 24) in order to separate abnormalities specific to cloning from effects of in vitro gamete and embryo manipulation. Nuclear transfer and IVF-fetuses, both derived from embryos cultured with 10% estrous cow serum, demonstrated significant fetal overgrowth. The increase in body weight relative to controls was similar for both groups (+22%, P < 0.001, and +19%, P < 0.001, respectively), but further analyses clearly separated the NT phenotype from the IVF phenotype. The NT-fetuses were characterized by a shorter crown-rump length but larger thorax circumference, which consequently produced a significantly reduced fetus length-to-thorax circumference ratio in comparison with IVF-fetuses and controls (-9% each, P < 0.0001). Absolute liver weight was significantly increased in NT- and IVF-fetuses (+62%, P < 0.0001, and +20%, P < 0.0001, respectively), but relative liver weight was increased only in NT-fetuses (+30%, P < 0.0001). Heart (P< 0.0001) and kidney (P = 0.0003) mass also showed disproportionate organomegaly in NT-fetuses only, but relative lung weight (NT, P = 0.263; IVF, P = 0.317) was not affected by either embryo technique. Transcript abundance for IGF2 and IGF2R genes were strongly correlated in muscle (r = 0.835, P < 0.0001), liver (r = 0.922, P < 0.0001), and lung (r = 0.772, P < 0.0001). The IGF2 and IGF2R transcript levels in muscle tissue from NT-fetuses were markedly reduced in comparison with both IVF-fetuses (-31%, P < 0.0001, and -41%, P < 0.0001, respectively) and controls (-31%, P < 0.0001, and -41%, P < 0.0001, respectively). In liver tissue, however, transcript levels for NT-fetuses were similar to those of controls, and IVF-fetuses showed markedly elevated, albeit non-significant, IGF2 (+86%, P = 0.0591) and IGF2R (+54%, P = 0.1305) mRNA levels relative to controls. Our data demonstrate that seemingly similar syndromes caused by NT or IVF procedures can be clearly partitioned with respect to phenotype and IGF2/IGF2R expression. 
