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Human Molecular Genetics Advance Access published online on May 18, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh157
© 2004 by Oxford University Press
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Article

The unique transcriptome through day 3 of human preimplantation development

Anthony T. Dobson 1*, Rajiv Raja 2, Michael J. Abeyta 3, Theresa Taylor 2, Shehua Shen 4, Christopher Haqq 5, Renee A. Reijo Pera 3

1 Center for Reproductive Sciences; Department of Obstetrics, Gynecology and Reproductive Sciences; Departments of Physiology and Urology; Programs in Human Genetics, Cancer Genetics, and Development and Stem Cell Biology; 513 Parnassus Avenue, Box 0556, University of California at San Francisco, San Francisco, CA 94143-0556, USA; Center for Reproductive Health; University of California at San Francisco, 2356 Sutter Street, San Francisco, CA 94115, USA
2 Arcturus Bioscience Inc., 400 Logue Avenue, Mountain View, California 94043, USA
3 Center for Reproductive Sciences; Department of Obstetrics, Gynecology and Reproductive Sciences; Departments of Physiology and Urology; Programs in Human Genetics, Cancer Genetics, and Development and Stem Cell Biology; University of California at San Francisco, San Francisco, California 94143, USA
4 Center for Reproductive Sciences; Department of Obstetrics, Gynecology and Reproductive Sciences; Departments of Physiology and Urology; Programs in Human Genetics, Cancer Genetics, and Development and Stem Cell Biology; University of California at San Francisco, San Francisco, California 94143, USA; Center for Reproductive Health; University of California at San Francisco, 2356 Sutter Street, San Francisco, CA 94115, USA
5 Comprehensive Cancer Center; Prostate Cancer Program; University of California at San Francisco, San Francisco, CA 94143, USA

* To whom correspondence should be addressed. E-mail: adobson{at}itsa.ucsf.edu.


  Abstract

Successful human development is dependent upon a cascade of events following fertilization. Unfortunately, knowledge of these critical events in humans is remarkably incomplete. Although hundreds of thousands of human embryos are cultured yearly at infertility centers worldwide, the vast majority fail to develop in culture or following transfer to the uterus. In this study, we sought to characterize global patterns of gene expression in individual, normal embryos during the first three days of embryonic life using microarrays; we then compared gene expression between normally growing and growth-arrested embryos using quantitative PCR. Our results documented several novel findings: First, we found that a complex pattern of gene expression exists; most genes that are transcriptionally modulated during the first three days following fertilization are not upregulated, as was previously thought, but are downregulated. Second, we observed that the majority of genes exhibiting differential expression during preimplantation development are of unknown identity and/or function. Third, we show that embryonic transcriptional programs are clearly established by day 3 following fertilization, even in embryos that arrested prematurely with 2-, 3- or 4-cells. This indicates that failure to activate transcription is not associated with the majority of human preimplantation embryo loss. Finally, taken together, these results provide the first global analysis of the human preimplantation embryo transcriptome, and demonstrate that RNA can be amplified from single oocytes and embryos for analysis by cDNA microarray technology, thus lending credence to additional studies of genetic regulation in these cell types, as well as in other small biological samples.


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