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Gene expression patterns associated with infertility in humans and rodent models
John C Rockett1, Pasquale Patrizio, Judith E Schmid
1Reproductive Toxicology Division (MD-72), National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Mutation Research
|May 4, 2004
Summary
Comparing gene expression in human and mouse testes identified key genes for male fertility. This research aids understanding of infertility causes, including environmental impacts.
Area of Science:
- Genomics
- Reproductive Biology
- Molecular Biology
Background:
- Genomic technologies like DNA arrays enable detailed molecular interaction studies.
- Gene expression profiling helps identify genes linked to various phenotypes.
- Understanding male fertility requires identifying critical genes and networks.
Purpose of the Study:
- To identify genes and gene networks crucial for male fertility.
- To compare testicular gene expression between normal and infertile human samples and infertile mouse models.
- To understand the molecular mechanisms underlying male infertility.
Main Methods:
- Utilized filter-based DNA arrays for testicular gene expression analysis.
- Examined gene expression from eight human testis biopsies.
- Analyzed three different infertile mouse models: atrichosis mutation, ataxia telangiectasia knockout, and CREMtau knockout.
Main Results:
- Identified 47 differentially expressed mouse genes (P <0.01) associated with male infertility, including those in DNA repair, glutathione metabolism, proteolysis, spermatogenesis, and stress response.
- Found 19 differentially expressed human genes (P<0.05) between normal and abnormal samples, linked to apoptosis, gonad development, proteolysis, and signal transduction.
- Discovered shared genes like glucose phosphate isomerase and similar metalloproteinase inhibitors (human TIMP3 and mouse Timp2) between species.
Conclusions:
- DNA microarrays are valuable for profiling testicular gene expression in infertile models and humans.
- This approach aids in understanding congenital infertility and environmentally induced infertility.
- Identified genes and networks provide insights into the molecular basis of male infertility.