Sperm DNA Methylation Analysis in Swine Reveals Conserved and Species-Specific Methylation Patterns and Highlights an Altered Methylation at the GNAS Locus in Infertile Boars.

Congras A, Yerle-Bouissou M, Pinton A, Vignoles F, Liaubet L, Ferchaud S, Acloque H

Male infertility is an increasing health issue in today's society, for both human or livestock populations. In livestock, male infertility slows the improvement of animal selection programs and agricultural productivity. There are increasing evidences that epigenetic marks play an important role in the production of good quality sperm. We therefore screened for specific or common epigenetic signatures of livestock infertility. To do so, we compared DNA methylation level in sperm DNA from fertile and infertile boars. We evaluated first the global level of sperm DNA methylation and found no difference between the two groups of boars. We then selected 42 loci of interest, most of them known to be imprinted in human or mice and assessed the imprinting status of 5 of them not previously described in swine tissues: WT1, CNTN3, IMPACT, QPCT and GRB10. DNA methylation level was then quantified in fertile and infertile boars, at these 42 loci. Results from fertile boars indicated that the methylation level of the selected loci is highly conserved between pig, human and mice, with a few exceptions, including the POU5F1 (OCT4) promoter and RTL1. Comparison between fertile and infertile boars revealed that one imprinted region, the GNAS locus, shows an increase in sperm DNA methylation in 4 out of 8 infertile boars with low semen quality. This increase in DNA methylation is associated with an altered expression of the genes belonging to the GNAS locus, suggesting a new role for GNAS in the proper formation of functional gametes.

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October, 2014



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