Key genetic and epigenetic factors contributed from male germ cell to early embryo: a novel bovine model

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The chromatin of mature spermatozoa is characterized by a dual protamine/nucleosome structure. Recent studies provide hints that somatic-like histones within the sperm exhibit specific 'codes' (posttranslational acetylatlon, mono-, di- or trimethylation on different lysine residues) and associate mainly with hypomethylated promoters of development relevant genes. The common hypothesis is that sperm histones and their 'codes' are transmitted to the oocyte together with the paternal haploid genome and are crucial for transcriptional activation during early embryogenesis. Using bovine germ cells and early embryos, we aim to establish a reproducible animal model for studies regarding genetic and epigenetic factors contributed from male germ cell to early embryo. A well accessible animal model will simplify the evaluation of risk candidate genes and mechanisms for impaired fertilization/early embryogenesis and, thus, for idiopathic male factor infertility. In the present study, the following aims will be addressed; 1) In bovine sperm, we will detect all genomic regions which associate with somatic-like histones and evaluate candidate genes for early development considering gene ontology; 2) The candidate genes will be further analyzed in oocytes and early embryo stages considering their promoter methylation and mRNA expression status; 3) To get a deeper insight in the epigenetic regulation during early embryogenesis, we will analyze the mRNA expression of key chromatin modifiers and pluripotency genes in bovine germ cells and early embryos; 4) For candidate genes evaluated in the bovine model, the human orthologous genes wilt be determined and analyzed in human sperm considering their fertility status.