429. Culture of mouse zygotes altered epigenetic states of the agouti viable yellow allele in the resulting progeny
A. Li A , H. Morgan A , X. Jin A , E. Whitelaw C and C. O.‘Neill A BA Human Reproduction Unit/Physiology, The University of Sydney, Sydney, NSW, Australia.
B Human Reproduction Unit, Royal North Shore Hospital, Sydney, NSW, Australia.
C Epigenetics Laboratory, Queensland Institute of Medical Research, Brisbane, Qld, Australia.
Reproduction, Fertility and Development 20(9) 109-109 https://doi.org/10.1071/SRB08Abs429
Published: 28 August 2008
Abstract
Epigenetic modification of the genome is one potential mechanism for the persistence of altered gene expression. Recent evidence indicates that the growth environment of the preimplantation embryo may have long-term consequences in the gene expression of progeny (Mahsoudi et al. 2007; Watkins et al. 2008). This study assessed whether culture of zygotes induced persistent epigenetic changes in gene expression. The agouti viable yellow (Avy) allele is epigenetically sensitive, and is a widely used model for studying epigenetic phenomena. It has active (hypomethyalted) and inactive (hypermethylated) epialleles. Progeny with an active epiallele have yellow fur; those with an inactive epiallele have an agouti coat. Some progeny are mosaics for the two epigenetic states and have a mottled coat color. Males (Avy/a C57BL/6) were mated to wildtype females (A/A FVB). Embryo treatments were: (1) zygotes collected and cultured for 96 h in Sydney IVF Media suite and transferred to day 3 pseudopregnant Swiss females; (2) blastocysts collected and transferred to recipients without being subjected to culture; (3) naturally mated females left to give birth without interventioin. The number, sex, genotype, and epi-phenotype of the resulting progeny were recorded. The culture of zygotes caused a significant shift in the expression of the epialleles compared with embryos that were transferred without culture (P = 0.014), or those born following natural matings (P < 0.001). Offspring that resulted from culture are more likely to have active epialleles, resulting in a higher proportion of progeny with yellow fur. The results of this study show that culture of mouse zygotes changed the expected expression of the Avy allele. This study provides evidence for the epigenetic basis for the long-term ‘memory’ of preimplantation embryo’s growth environment, and for robust and readily accessible methodology for addressing the underlying molecular bases for this phenomenon.
(1) Mahsoudi B, Li A, O’Neill C. Assessment of the Long-Term and Transgenerational Consequences of Perturbing Preimplantation Embryo Development in Mice. Biol Reprod 2007; 77: 889–896.
(2) Watkins AJ, Ursell E, Panton R, Papenbrock T, Hollis L, Cunningham C, Wilkins A, Perry VH, Sheth B, Kwong WY, Eckert JJ, Wild AE, Hanson MA, Osmond C, Fleming TP. Adaptive responses by mouse early emb.