Investigations on Transgenerational Epigenetic Response Down the Male Line in F2 Pigs

We investigated the nutritional effects on carcass traits, gene expression and DNA methylation in a three generation Large White pig feeding experiment. A group of experimental (E) F0 boars were fed a standard diet supplemented with high amounts of methylating micronutrients whereas a control group (C) of F0 boars received a standard diet. These differentially fed F0 boars sired F1 boars which then sired 60 F2 pigs. Carcass traits were compared between 36 F2 descendants of E F0 boars and 24 F2 descendants of C F0 boars. The two F2 offspring groups differed with respect to backfat percentage (P = 0.03) and tended to differ with respect to adipose tissue (P = 0.09), fat thickness at the 10th rib (P = 0.08) and at the croup (P = 0.09) as well as percentages of shoulder (P = 0.07). Offspring from the experimental F0 boars had a higher percentage of shoulder and were leaner compared to the control group. Gene expression profiles showed significant twofold differences in mRNA level between 8 C F2 offspring and 8 E F2 offspring for 79, 64 and 53 genes for muscle, liver and kidney RNA, respectively. We found that in liver and muscle respective pathways of lipid metabolism and metabolic pathway were over-represented for the differentially expressed genes between these groups. A DNA methylation analysis in promoters of differentially expressed genes indicated a significant difference in DNA methylation at the IYD gene. If these responses on carcass traits, gene expression and DNA methylation withstand verification and can indeed be attributed to transgenerational epigenetic inheritance, it would open up pioneering application in pork production and would have implications for human health.

[1]  V. Rakyan,et al.  Transgenerational inheritance of epigenetic states at the murine AxinFu allele occurs after maternal and paternal transmission , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Matthew D. Schultz,et al.  Transgenerational Epigenetic Instability Is a Source of Novel Methylation Variants , 2011, Science.

[3]  Haruhiko Koseki,et al.  Dynamic Reprogramming of DNA Methylation at an Epigenetically Sensitive Allele in Mice , 2006, PLoS genetics.

[4]  N. Youngson,et al.  Transgenerational epigenetic effects. , 2008, Annual review of genomics and human genetics.

[5]  A. Oevermann,et al.  Neurological signs in pigs supplemented orally with pharmacological amounts of B vitamins from one to 10 months of age , 2009, Veterinary Record.

[6]  W. Reik,et al.  Epigenetic Reprogramming in Mammalian Development , 2001, Science.

[7]  R. Kodell,et al.  Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/a mice , 1998, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[8]  M. Pembrey,et al.  Sex-specific, male-line transgenerational responses in humans , 2006, European Journal of Human Genetics.

[9]  R. Waterland,et al.  Maternal methyl supplements increase offspring DNA methylation at Axin fused , 2006, Genesis.

[10]  K. Wagner,et al.  RNA induction and inheritance of epigenetic cardiac hypertrophy in the mouse. , 2008, Developmental cell.

[11]  David I. K. Martin,et al.  Germ-line epigenetic modification of the murine Avy allele by nutritional supplementation , 2006, Proceedings of the National Academy of Sciences.

[12]  G. Bee.  Effect of early gestation feeding, birth weight, and gender of progeny on muscle fiber characteristics of pigs at slaughter. , 2004, Journal of animal science.

[13]  S. Edvinsson,et al.  Cardiovascular and diabetes mortality determined by nutrition during parents' and grandparents' slow growth period , 2002, European Journal of Human Genetics.

[14]  Michael K. Skinner,et al.  Epigenetic transgenerational actions of environmental factors in disease etiology , 2010, Trends in Endocrinology & Metabolism.

[15]  Board on Agriculture,et al.  Nutrient requirements of swine , 1964 .

[16]  David I. K. Martin,et al.  Epigenetic inheritance at the agouti locus in the mouse , 1999, Nature Genetics.

[17]  P. Gounon,et al.  RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse , 2006, Nature.

[18]  Michael K. Skinner,et al.  Epigenetic Transgenerational Actions of Endocrine Disruptors and Male Fertility , 2005, Science.

[19]  R. Jirtle,et al.  Environmental epigenomics and disease susceptibility , 2007, Nature Reviews Genetics.

[20]  Relationship of porcine IGF2 imprinting status to DNA methylation at the H19 DMD and the IGF2 DMRs 1 and 2 , 2011, BMC Genetics.

[21]  Eva Jablonka,et al.  Transgenerational Epigenetic Inheritance: Prevalence, Mechanisms, and Implications for the Study of Heredity and Evolution , 2009, The Quarterly Review of Biology.

[22]  S. Chong,et al.  Epigenetic germline inheritance. , 2004, Current opinion in genetics & development.

[23]  Alex E. Lash,et al.  Gene Expression Omnibus: NCBI gene expression and hybridization array data repository , 2002, Nucleic Acids Res..

[24]  Robert A. Waterland,et al.  Transposable Elements: Targets for Early Nutritional Effects on Epigenetic Gene Regulation , 2003, Molecular and Cellular Biology.

[25]  Board on Agriculture,et al.  Vitamin Tolerance of Animals , 1987 .

[26]  Zhiping Weng,et al.  Paternally Induced Transgenerational Environmental Reprogramming of Metabolic Gene Expression in Mammals , 2010, Cell.