Epigenetic Dysregulation: From Somatic Cell Nuclear Transfer (SCNT) to Intrauterine Growth Restriction (IUGR)

Jorge Piedrahita
Molecular Biomedical Sciences;

Studies in multiple species have demonstrated the drastic developmental consequences that can result due to SCNT. Yet, the severity of the phenotype depends on the species being studied and ranges from severe effects in cattle and sheep to mild phenotypes in swine. We have shown that in the bovine cloning results in severe disregulation of selected imprinted genes. Additionally we have demonstrated that the severity of the disregulation is greater in placental that fetal tissues. This has lead us to try and understand the role of imprinted genes in normal and abnormal placenta functions. This is being accomplished both in a porcine uniparental model as well as in normal versus IUGR placentas. Results to date indicate that there are two types of imprinted genes, ones that are very tightly regulated and can be described as absolute monoallelic expressed and others that have a more relaxed regulation where the "silent" allele can be expressed at varying degrees (supported by NIH HL51587 and USDA-CSREES Functional Genomics 524383).

REFERENCES:

  1. Archer GS, Dindot S, Friend TH, Walker S, Zaunbrecher G, Lawhorn B, Piedrahita JA. 2003. Hierarchical Phenotypic and Epigenetic Variation in Cloned Swine. Biol. Reprod. 69:430-436.

  2. Dindot S, Kent KC, Evers B, Loskutoff N, Womack J and Piedrahita JA. 2004. Conservation of genomic imprinting at the XIST, IGF2, and GTL2 loci in the bovine. Mammalian Genome 15:828-833.

  3. Dindot S, Farin C, Farin P, Miles J, Walker S, Long C, and Piedrahita JA. 2004. Epigenetic and genomic imprinting analysis in nuclear transfer derived Bos gaurus/Bos taurus hybrid fetuses. Biol. Reprod. 71:470-478.

  4. Mir B, Zaunbrecher G, Archer GS, Friend T, and Piedrahita JA. 2005. Progeny of somatic cell nuclear transfer (SCNT) clones is phenotypically similar to non-cloned pigs. Cloning and Stem Cells. 7:119-125.