Epigenetic disturbances in in vitro cultured gametes and embryos: implications for human assisted reproduction Nady el Hajj, Ph.D., Thomas Haaf, M.D.

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Epigenetic disturbances in in vitro cultured gametes and embryos: implications for human assisted reproduction Nady el Hajj, Ph.D., Thomas Haaf, M.D. Fertility and Sterility Volume 99, Issue 3, Pages 632-641 (March 2013) DOI: 10.1016/j.fertnstert.2012.12.044 Copyright © 2013 American Society for Reproductive Medicine Terms and Conditions

Figure 1 Phenotyic effects of assisted reproductive technologies in humans and animal models. Fertility and Sterility 2013 99, 632-641DOI: (10.1016/j.fertnstert.2012.12.044) Copyright © 2013 American Society for Reproductive Medicine Terms and Conditions

Figure 2 Epigenetic abnormalities associated with in vitro culture (IVC) and maturation (IVM) of human, bovine, and murine oocytes. The schematic drawing on the top indicates the DNA methylation dynamics during female (red line) and male (blue line) germ-cell development. Genes with aberrant DNA methylation patterns in cultured oocytes are marked in red, genes with normal methylation imprints are marked in black. H3K9Ac refers to insufficient global histone-3 lysine-9 deacetylation. Arrows indicate long-term IVM starting with preantral follicles and short-term IVM starting with GV oocytes. PGC = primordial germ cell; S = spermatogonia; O = oogonia; PL = preleptotene; L = leptotene; Z = zygotene; P = pachytene; D = diplotene; NG = nongrowing oocyte; RS = round spermatid; G = growing oocyte; GV = germinal vesicle oocyte; MII = metaphase II oocyte. Fertility and Sterility 2013 99, 632-641DOI: (10.1016/j.fertnstert.2012.12.044) Copyright © 2013 American Society for Reproductive Medicine Terms and Conditions

Figure 3 Epigenetic (DNA methylation and histone modification) abnormalities associated with human and mouse embryo culture. The schematic drawing on the top indicates the DNA methylation dynamics of the maternal (red line) and paternal (blue line) genome during preimplantation development. Genes with aberrant DNA methylation patterns in cultured embryos are highlighted in red, genes with normal methylation imprints are marked in black. Similarly, aberrant histone modifications are highlighted in red. Solid arrows indicate beginning and end of embryo culture. Dashed arrows indicate embryo culture to different stages in the same study. Fertility and Sterility 2013 99, 632-641DOI: (10.1016/j.fertnstert.2012.12.044) Copyright © 2013 American Society for Reproductive Medicine Terms and Conditions