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GENE EXPRESSION PATTERNS ASSOCIATED WITH INFERTILITY IN HUMAN AND RODENT MODELS
Citation:
Rockett, J C., M. S. Ricci, P. Patrizio, J E. Schmid, N. B. Hecht, AND D J. Dix. GENE EXPRESSION PATTERNS ASSOCIATED WITH INFERTILITY IN HUMAN AND RODENT MODELS. MUTATION RESEARCH 549(1-2):225-40, (2004).
Impact/Purpose:
To identify genes and gene networks critical for male fertility
Description:
Modern genomic technologies such as DNA arrays provide the means to investigate molecular interactions at an unprecedented level, and arrays have been used to carry out gene expression profiling as a means of identifying candidate genes involved in molecular mechanisms underlying a variety of phenotypes. By comparing gene expression profiles from normal and abnormal human testes with those from comparable infertile mouse models, we endeavored to identify genes and gene networks critical for male fertility. We used commercially available filter-based DNA arrays to analyze testicular gene expression from eight human testis biopsies and three different infertile mouse models (atrichosis mutation, ataxia telangiectasiaknockout and CREMtau knockout). Forty seven mouse genes exhibited differential testicular gene expression (p<0.01) associated with male infertility. These included genes involved in DNA repair (Vim, Rad23A, Rad23B), glutathione metabolism (Gsr , Gstp 1, Mgst1), proteolysis (Ace, Casp1, Ctsd), spermatogenesis (Prlr, Tmsb4 and Zfp-37) and stress response (Hsp 1, Osp94 ). Nineteen human genes were different (p<0.05) between normal and abnormal samples, including those associated with apoptosis (GADD45), gonad development (SOX9), proteolysis (PSMC3, SPINK2, TIMP3, UBE213) and signal transduction (DLK1, NAP4, S100A10). Direct comparison of differentially expressed human and mouse genes identified glucose phosphate isomerase, and the highly similar human tissue inhibitor of metalloproteinase 3 (TIMP3) and mouse Timp2. Using DNA microarrays to profile gene expression in testes from infertile animal models and humans will be useful for understanding congenital infertility, and also infertility caused by environmental exposures where the same genes and molecular mechanisms are involved.