HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 79/4/618    most recent biolreprod.108.068213v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal My Folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Morgan, H. D. Articles by O'Neill, C. Search for Related Content PubMed PubMed Citation Articles by Morgan, H. D. Articles by O'Neill, C. Agricola Articles by Morgan, H. D. Articles by O'Neill, C.

The Culture of Zygotes to the Blastocyst Stage Changes the Postnatal Expression of an Epigentically Labile Allele, Agouti Viable Yellow, in Mice¹

Human Reproduction Unit, Royal North Shore Hospital, Disciplines of Medicine³ and Physiology,⁴ Faculty of Medicine, University of Sydney, Sydney, 2065 New South Wales, Australia Epigenetics Laboratory,⁵ Queensland Institute of Medical Research, Brisbane, 4006 Queensland, Australia

ABSTRACT

Restricting the growth of the embryo can cause adverse whole-of-life changes in an organism's homeostasis. Such adverse long-term consequences may occur even when growth restriction occurs only during the preimplantation period. The molecular basis for these long-term effects has not been defined, although an epigenetic mechanism is suspected. Some loci seem to be more sensitive to epigenetic perturbation than others, and the agouti viable yellow allele (A^vy) is the best studied example of this. It has active (hypomethylated) and inactive (hypermethylated) epialleles. This study used the A^vy model to show that growth restriction of preimplantation embryos, as provided by culture of zygotes, induced persistent epigenetic changes that resulted in altered postnatal phenotype. C57BL/6 A^vy/a males were mated to ovulation-induced FVB/N females, and then either zygotes were collected and cultured for 96 h and the resulting blastocysts were transferred to pseudopregnant recipient females, blastocysts were collected from females and transferred without embryo culture, or pregnancy was allowed to proceed after mating without intervention. Culture was in a commercial human in vitro fertilization media. The proportion of pups expressing the active (hypomethylated) epiallele and yellow coat was significantly higher following zygote culture compared to embryos that were transferred without culture (P = 0.014) or natural matings (P < 0.001). There was no difference in expression of the active epiallele in pups resulting from embryo transfer (without culture) compared to natural matings. These results show for the first time that the preimplantation embryo's growth environment can affect the postnatal expression of a defined epigenetically sensitive allele.

early development, embryo, environment, epigenetic modification, epigenetics, gene regulation, in vitro embryo culture, phenotypic variation, preimplantation development

¹Supported by a National Health and Medical Research Council, Australia, C.J. Martin Fellowship to H.M. and a National Health and Medical Research Council, Australia, Project Grant to C.O.

Correspondence: ²Chris O'Neill, Human Reproduction Unit, Royal North Shore Hospital, University of Sydney, Sydney, 2065 NSW, Australia. FAX: 61 2 9926 6343; e-mail: chriso{at}med.usyd.edu.au

This article has been cited by other articles:

				J.J. Eppig, M.J. O'Brien, K. Wigglesworth, A. Nicholson, W. Zhang, and B.A. King Effect of in vitro maturation of mouse oocytes on the health and lifespan of adult offspring Hum. Reprod., April 1, 2009; 24(4): 922 - 928. [Abstract] [Full Text] [PDF]

				B. T. Heijmans, E. W. Tobi, A. D. Stein, H. Putter, G. J. Blauw, E. S. Susser, P. E. Slagboom, and L. H. Lumey Persistent epigenetic differences associated with prenatal exposure to famine in humans PNAS, November 4, 2008; 105(44): 17046 - 17049. [Abstract] [Full Text] [PDF]