title: High Frequency of Imprinted Methylation Errors in Human Preimplantation Embryos.
abstract: Assisted reproductive technologies (ARTs) represent the best chance for infertile couples to conceive, although increased risks for morbidities exist, including imprinting disorders. This increased risk could arise from ARTs disrupting genomic imprints during gametogenesis or preimplantation. The few studies examining ART effects on genomic imprinting primarily assessed poor quality human embryos. Here, we examined day 3 and blastocyst stage, good to high quality, donated human embryos for imprinted SNRPN, KCNQ1OT1 and H19 methylation. Seventy-six percent day 3 embryos and 50% blastocysts exhibited perturbed imprinted methylation, demonstrating that extended culture did not pose greater risk for imprinting errors than short culture. Comparison of embryos with normal and abnormal methylation didn't reveal any confounding factors. Notably, two embryos from male factor infertility patients using donor sperm harboured aberrant methylation, suggesting errors in these embryos cannot be explained by infertility alone. Overall, these results indicate that ART human preimplantation embryos possess a high frequency of imprinted methylation errors.
authors.affiliation: Department of Obstetrics &Gynecology, University of Western Ontario, Schulich School of Medicine and Dentistry, London, Ontario, Canada.|Department of Biochemistry, University of Western Ontario, Schulich School of Medicine and Dentistry, London, Ontario, Canada.|Children's Health Research Institute, London, Ontario, Canada.
authors.forename: Carlee R
authors.initials: CR
authors.lastname: White
authors.affiliation: Department of Obstetrics &Gynecology, University of Western Ontario, Schulich School of Medicine and Dentistry, London, Ontario, Canada.|Department of Biochemistry, University of Western Ontario, Schulich School of Medicine and Dentistry, London, Ontario, Canada.|Children's Health Research Institute, London, Ontario, Canada.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Denomme
authors.affiliation: Department of Obstetrics &Gynecology, University of Western Ontario, Schulich School of Medicine and Dentistry, London, Ontario, Canada.|The Fertility Clinic, London Health Sciences Centre, London, Ontario, Canada.
authors.forename: Francis R
authors.initials: FR
authors.lastname: Tekpetey
authors.affiliation: Department of Obstetrics &Gynecology, University of Western Ontario, Schulich School of Medicine and Dentistry, London, Ontario, Canada.|The Fertility Clinic, London Health Sciences Centre, London, Ontario, Canada.
authors.forename: Valter
authors.initials: V
authors.lastname: Feyles
authors.affiliation: Department of Obstetrics &Gynecology, University of Western Ontario, Schulich School of Medicine and Dentistry, London, Ontario, Canada.|The Fertility Clinic, London Health Sciences Centre, London, Ontario, Canada.
authors.forename: Stephen G A
authors.initials: SG
authors.lastname: Power
authors.affiliation: Department of Obstetrics &Gynecology, University of Western Ontario, Schulich School of Medicine and Dentistry, London, Ontario, Canada.|Department of Biochemistry, University of Western Ontario, Schulich School of Medicine and Dentistry, London, Ontario, Canada.|Children's Health Research Institute, London, Ontario, Canada.
authors.forename: Mellissa R W
authors.initials: MR
authors.lastname: Mann
mesh_terms: D000328:Adult; D001755:Blastocyst / Q000378:metabolism*; D019175:DNA Methylation; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects*; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism; D055517:snRNP Core Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C094335:H19 long non-coding RNA; C485621:KCNQ1OT1 long non-coding RNA, human; D024642:Potassium Channels, Voltage-Gated; D062085:RNA, Long Noncoding; C526417:SNRPN protein, human; D055517:snRNP Core Proteins