Human Molecular Genetics Advance Access originally published online on August 18, 2004
Human Molecular Genetics 2004 13(19):2263-2278; doi:10.1093/hmg/ddh241
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Human Molecular Genetics, Vol. 13, No. 19 © Oxford University Press 2004; all rights reserved
Age-associated alteration of gene expression patterns in mouse oocytes
Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, National Institutes of Health, 333 Cassell Drive, Suite 3000, Baltimore, MD 21224, USA
Received May 9, 2004; Accepted July 20, 2004
Decreasing oocyte competence with maternal aging is a major factor in human infertility. To investigate the age-dependent molecular changes in a mouse model, we compared the expression profiles of metaphase II oocytes collected from 5- to 6-week-old mice with those collected from 42- to 45-week-old mice using the NIA 22K 60-mer oligo microarray. Among approximately 11 000 genes whose transcripts were detected in oocytes, about 5% (530) showed statistically significant expression changes, excluding the possibility of global decline in transcript abundance. Consistent with the generally accepted view of aging, the differentially expressed genes included ones involved in mitochondrial function and oxidative stress. However, the expression of other genes involved in chromatin structure, DNA methylation, genome stability and RNA helicases was also altered, suggesting the existence of additional mechanisms for aging. Among the transcripts decreased with aging, we identified and characterized a group of new oocyte-specific genes, members of the human NACHT, leucine-rich repeat and PYD-containing (NALP) gene family. These results have implications for aging research as well as for clinical ooplasmic donation to rejuvenate aging oocytes.
* To whom correspondence should be addressed. Tel: +1 4105588359; Fax: +1 4105588331; Email: kom{at}grc.nia.nih.gov
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