Skip Navigation


Mol. Hum. Reprod. Advance Access originally published online on October 11, 2005
Molecular Human Reproduction 2005 11(9):631-640; doi:10.1093/molehr/gah230
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
11/9/631    most recent
gah230v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (20)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Li, T.
Right arrow Articles by Hoffman, A. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, T.
Right arrow Articles by Hoffman, A. R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. 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

IVF results in de novo DNA methylation and histone methylation at an Igf2-H19 imprinting epigenetic switch

Tao Li1,2,*, Thanh H. Vu1,2,*, Gary A. Ulaner1,2,*, Eva Littman3,*, Jian-Qun Ling1,2, Hui-Ling Chen1,2, Ji-Fan Hu1,2, Barry Behr3, Linda Giudice3 and Andrew R. Hoffman1,2,4

1Medical Service, VA Palo Alto Health Care System, 2Department of Medicine and 3Department of Gynecology & Obstetrics, Stanford University, Palo Alto, CA, USA

4 To whom correspondence should be addressed at: Medical Service, VA Palo Alto Medical Center, 3801 Miranda Avenue, Palo Alto, CA 94304, USA. E-mail: arhoffman{at}stanford.edu

Recent studies suggest that IVF and assisted reproduction technologies (ART) may result in abnormal genomic imprinting, leading to an increased frequency of Angelman syndrome (AS) and Beckwith–Weidemann syndrome (BWS) in IVF children. To learn how ART might alter the epigenome, we examined morulas and blastocysts derived from C57BL/6J X M. spretus F1 mice conceived in vivo and in vitro and determined the allelic expression of four imprinted genes: Igf2, H19, Cdkn1c and Slc221L. IVF-derived mouse embryos that were cultured in human tubal fluid (HTF) (Quinn’s advantage) media displayed a high frequency of aberrant H19 imprinting, whereas in vivo and IVF embryos showed normal maternal expression of Cdkn1c and normal biallelic expression of Igf2 and Slc221L. Embryonic stem (ES) cells derived from IVF blastocysts also showed abnormal Igf2/H19 imprinting. Allele-specific bisulphite PCR reveals abnormal DNA methylation at a CCCTC-binding factor (CTCF) site in the imprinting control region (ICR), as the normally unmethylated maternal allele acquired a paternal methylation pattern. Chromatin immunoprecipitation (ChIP) assays indicate an increase of lysine 4 methylation (dimethyl Lys4-H3) on the paternal chromatin and a gain in lysine 9 methylation (trimethyl Lys9-H3) on the maternal chromatin at the same CTCF-binding site. Our results indicate that de novo DNA methylation on the maternal allele and allele-specific acquisition of histone methylation lead to aberrant Igf2/H19 imprinting in IVF-derived ES cells. We suggest that ART, which includes IVF and various culture media, might cause imprinting errors that involve both aberrant DNA methylation and histone methylation at an epigenetic switch of the Igf2-H19 gene region.

Key words: DNA methylation/embryonic stem cells/H19/Igf2/imprinting/IVF

* The authors equally contributed to this work.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum ReprodHome page
D. J. Amor and J. Halliday
A review of known imprinting syndromes and their association with assisted reproduction technologies
Hum. Reprod., August 14, 2008; (2008) den310v1.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
X. Qiu, T. H. Vu, Q. Lu, J. Q. Ling, T. Li, A. Hou, S. K. Wang, H. L. Chen, J. F. Hu, and A. R. Hoffman
A Complex Deoxyribonucleic Acid Looping Configuration Associated with the Silencing of the Maternal Igf2 Allele
Mol. Endocrinol., June 1, 2008; 22(6): 1476 - 1488.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
M. E. Torres-Padilla
Cell identity in the preimplantation mammalian embryo: an epigenetic perspective from the mouse
Hum. Reprod., June 1, 2008; 23(6): 1246 - 1252.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. Wyman, A. B. Pinto, R. Sheridan, and K. H. Moley
One-Cell Zygote Transfer from Diabetic to Nondiabetic Mouse Results in Congenital Malformations and Growth Retardation in Offspring
Endocrinology, February 1, 2008; 149(2): 466 - 469.
[Abstract] [Full Text] [PDF]

Home page
 ReproductionHome page
G. Giritharan, S. Talbi, A. Donjacour, F. Di Sebastiano, A. T Dobson, and P. F Rinaudo
Effect of in vitro fertilization on gene expression and development of mouse preimplantation embryos
Reproduction, July 1, 2007; 134(1): 63 - 72.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
T. M. Price, S. K. Murphy, and E. V. Younglai
Perspectives: The Possible Influence of Assisted Reproductive Technologies on Transgenerational Reproductive Effects of Environmental Endocrine Disruptors
Toxicol. Sci., April 1, 2007; 96(2): 218 - 226.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y.-C. Lu, J. Song, H.-Y. Cho, G. Fan, K. K. Yokoyama, and R. Chiu
Cyclophilin A Protects Peg3 from Hypermethylation and Inactive Histone Modification
J. Biol. Chem., December 22, 2006; 281(51): 39081 - 39087.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.