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Hum. Reprod. Advance Access originally published online on August 21, 2006
Human Reproduction 2007 22(1):26-35; doi:10.1093/humrep/del316
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Aberrant DNA methylation of imprinted loci in superovulated oocytes

A. Sato1,*, E. Otsu1,*, H. Negishi1, T. Utsunomiya1 and T. Arima2,3

1 St Luke Clinic, Tsumori, Oita, Japan and 2 Department of Molecular Genetics, Division of Molecular and Cell Therapeutics, Medical Institute of Bioregulation, Kyusyu University, Beppu, Oita, Japan

3 To whom correspondence should be addressed at: Department of Molecular Genetics, Division of Molecular and Cell Therapeutics, Medical Institute of Bioregulation, Kyusyu University, 4546, Tsurumihara, Beppu, Oita 874-0838, Japan. E-mail: tarima{at}tsurumi.beppu.kyushu-u.ac.jp

BACKGROUND: There is an increased incidence of rare imprinting disorders associated with assisted reproduction technologies (ARTs). The sex-specific epigenetic modifications that are imposed during gametogenesis act as a primary imprint to distinguish maternal and paternal alleles. The most likely candidate for the gametic mark is DNA methylation. However, the timing of DNA methylation acquisition in adult oocytogenesis and the effects of superovulation are unknown. METHODS: We examined the maternal methylation of PEG1(MEST), LIT1(KCNQ1OT1) and ZAC(PLAGL1) and the paternal methylation of H19 in adult growing oocytes of humans and mice and compared them with the methylation status of mouse neonatal growing oocytes by using bisulphite sequencing. Furthermore, we examined the effects of superovulation in the human and mouse. RESULTS: Maternal methylation of these genes has already been initiated to some extent in adult human and mouse non-growing oocytes but not in mouse neonates. In addition, the methylation dynamics during adult human and mouse oocyte development changed more gradually than those during neonatal oocyte development. Furthermore, we found the demethylation of PEG1 in growing oocytes from some ART-treated infertile women and a gain in the methylation of H19. We also detected methylation changes in superovulated mice. CONCLUSION: Our studies in the human and mouse suggest that superovulation can lead to the production of oocytes without their correct primary imprint and highlight the need for more research into ARTs.

Key words: ART/DNA methylation/genomic imprinting/human adult oocyte/superovulation

* These authors contributed equally to this work.


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