Epigenetic risks of assisted reproductive technologies (ART)
Although assisted reproduction has become a routine practice for human infertility treatment, the etiology of the increased risks for medical problems in ART-conceived children is still poorly understood. Data from mouse experiments and in vitro production of cattle and sheep provide strong evidence that imprint establishment in late oocyte stages and reprogramming of the two germline genomes for somatic development after fertilization are vulnerable to environmental cues. In vitro culture and maturation of oocytes, superovulation and embryo culture all represent artificial intrusions upon the natural development, which can influence the epigenome of the exposed germ cells and embryos. The ART-induced changes are not only critical for embryonal, placental, and fetal development. Accumulating evidence suggests that adverse factors in the periconceptionel period also can have long-lasting effects on the epigenome of the resultant offspring and disease susceptibilities later in life. We analyze the effects of different ART on epigenetic reprogramming in murine and bovine germ cells/embryos and, to the extent it is possible, in human miscarriages and newborns. Although there are considerable species differences in germ-cell and embryo development, in particular between humans and mice, the experimental findings in different animal models must be considered as serious.
El Hajj N, Zechner U, Schneider E, Tresch A, Gromoll J, Hahn T, Schorsch M, Haaf T. Methylation status of imprinted genes and repetitive elements in sperm DNA from infertile males. Sex. Dev. 5, 60-69 (2011).
Heinzmann J, Hansmann T, Herrmann D, Wrenzycki C, Zechner U, Haaf T, Niemann H. Epigenetic profile of developmentally important genes in bovine oocytes. Mol. Reprod. Dev. 78, 188-201 (2011).
El Hajj N, Trapphoff T, Linke M, May A, Hansmann T, Kuhtz J, Reifenberg K, Heinzmann J, Niemann H, Daser A, Eichenlaub-Ritter U, Zechner U, Haaf T. Limiting dilution bisulfite (pyro)sequencing reveals parent-specific methylation patterns in single early mouse embryos and bovine oocytes. Epigenetics 6, 1176-1188 (2011).
Trapphoff T, El Hajj N, Zechner U, Haaf T, Eichenlaub-Ritter U. DNA integrity, growth pattern, spindle formation, chromosomal constitution and imprinting patterns of oocytes from vitrified pre-antral follicles. Hum. Reprod. 25, 3025-3042 (2010).
Pliushch G, Schneider E, Weise D, El Hajj N, Tresch A, Seidmann L, Coerdt W, Müller AM, Zechner U, Haaf T. Extreme methylation values of imprinted genes in human abortions and stillbirths. Am. J. Pathol. 176, 1084-1090 (2010).
Zechner U, Pliushch G, Schneider E, El Hajj N, Tresch A, Shufaro Y, Seidmann L, Coerdt W, Müller AM, Haaf T. Quantitative methylation analysis of developmentally important genes in human pregnancy losses after ART and spontaneous conception. Mol. Hum. Reprod. 16, 704-713 (2010).