Coordinated transcriptional regulation patterns associated with infertility phenotypes in men

• Published in: Journal of medical genetics 2007-08, Vol.44 (8), p.498-508
• Main Authors: Ellis, Peter J I, Furlong, Robert A, Conner, Sarah J, Kirkman-Brown, Jackson, Afnan, Masoud, Barratt, Christopher, Griffin, Darren K, Affara, Nabeel A
• Format: Article
• Language: English
• Subjects: ACU; Assisted Conception Unit; Azoospermia - genetics; Biological and medical sciences; Biopsy; Birth control; CTFR; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; cystic fibrosis transmembrane regulator; Cytokines - blood; Exons; false discovery rate; FDR; follicle-stimulating hormone; FSH; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation; gene ontology; Genetics of eukaryotes. Biological and molecular evolution; Genomes; germ cell; Gynecology. Andrology. Obstetrics; Histology; Humans; Infertility; Infertility, Male - genetics; Infertility, Male - pathology; Interferon gamma Receptor; Male; Medical genetics; Medical sciences; Membranes; microarray; Molecular and cellular biology; Morphology; Oligonucleotide Array Sequence Analysis; Original; Patients; PDA; Phenotype; principal components analysis; Receptors, Interferon - genetics; Reproductive Techniques, Assisted; Reverse Transcriptase Polymerase Chain Reaction; Rodents; SCO; Sertoli-cell only; Sperm; Sperm Motility; Spermatogenesis; Sterility. Assisted procreation; Studies; TESE; testicular sperm extraction; testis; Transcription, Genetic; Vas Deferens - pathology; Vasectomy; Women
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.2007.049650

Introduction: Microarray gene-expression profiling is a powerful tool for global analysis of the transcriptional consequences of disease phenotypes. Understanding the genetic correlates of particular pathological states is important for more accurate diagnosis and screening of patients, and thus for suggesting appropriate avenues of treatment. As yet, there has been little research describing gene-expression profiling of infertile and subfertile men, and thus the underlying transcriptional events involved in loss of spermatogenesis remain unclear. Here we present the results of an initial screen of 33 patients with differing spermatogenic phenotypes. Methods: Oligonucleotide array expression profiling was performed on testis biopsies for 33 patients presenting for testicular sperm extraction. Significantly regulated genes were selected using a mixed model analysis of variance. Principle components analysis and hierarchical clustering were used to interpret the resulting dataset with reference to the patient history, clinical findings and histological composition of the biopsies. Results: Striking patterns of coordinated gene expression were found. The most significant contains multiple germ cell-specific genes and corresponds to the degree of successful spermatogenesis in each patient, whereas a second pattern corresponds to inflammatory activity within the testis. Smaller-scale patterns were also observed, relating to unique features of the individual biopsies.