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: 79/4/638    most recent biolreprod.108.069096v1 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 Han, Z. Articles by Latham, K. E. Search for Related Content PubMed PubMed Citation Articles by Han, Z. Articles by Latham, K. E. Agricola Articles by Han, Z. Articles by Latham, K. E.

Hybrid Vigor and Transgenerational Epigenetic Effects on Early Mouse Embryo Phenotype¹

The Fels Institute for Cancer Research and Molecular Biology,³ and Departments of Pathology⁴ and Biochemistry,⁵ Temple University School of Medicine, Philadelphia, Pennsylvania 19140-5101

ABSTRACT

Mouse embryos display a strain-dependent propensity for blastomere cytofragmentation at the two-cell stage. The maternal pronucleus exerts a predominant, transcription-dependent effect on this phenotype, with lesser effects of the ooplasm and the paternal pronucleus. A parental origin effect has been observed as an inequality in the cytofragmentation rate of embryos produced through genetic crosses of reciprocal F₁ hybrid females. To understand the basis for this, we conducted an extensive series of pronuclear transfer studies employing different combinations of inbred and F₁ hybrid maternal and paternal genotypes. We find that the parental origin effect is the result of a transgenerational epigenetic modification, whereby the inherited maternal grandpaternal contribution interacts with the fertilizing paternal genome and the ooplasm. This result indicates that some epigenetic information related to grandparental origins of chromosomes (i.e., imprinting of chromosomes in the mother) is retained through oogenesis and transmitted to progeny, where it affects gene expression from the maternal pronucleus and subsequent embryo phenotype. These results reveal for the first time that mammalian embryonic development can be affected by the epigenotype of at least three individuals. Additionally, we observe a significant suppression of fragmentation by F₁ hybrid ooplasm when it is separated from the F₁ hybrid maternal pronucleus. This latter effect is a striking example of heterosis in the early mammalian embryo, and it provides a new opportunity for examining the molecular mechanisms of heterosis. These results are relevant to our understanding of the mechanisms of epigenetic effects on development and the possible fertility effects of genetic and epigenetic interactions in reproductive medicine.

apoptosis, cytofragmentation, embryo, gene regulation, genomic imprinting, heterosis, mitochondria, nuclear transfer, oocyte development, parental origin effects, superovulation, transgenerational effect

¹Supported in part by grants from the National Institutes of Health, National Institute for Child Health and Human Development and National Center for Research Resources (HD41440 and RR15253 to K.E.L., and HD48730 and HD34508 to C.S.).

Correspondence: ²Correspondence: Keith E. Latham, 3307 N. Broad St., Philadelphia, PA 19140-5101. FAX: 215 707 1454; e-mail: klatham{at}temple.edu

This article has been cited by other articles:

				Y. Cheng, K. Wang, L. D. Kellam, Y. S. Lee, C.-G. Liang, Z. Han, N. R. Mtango, and K. E. Latham Effects of Ooplasm Manipulation on DNA Methylation and Growth of Progeny in Mice Biol Reprod, March 1, 2009; 80(3): 464 - 472. [Abstract] [Full Text] [PDF]