Coordinated transcriptional regulation patterns associated with infertility phenotypes in men.
BACKGROUND
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.
Ellis
Peter J I
PJ
Mammalian Molecular Genetics Group, University of Cambridge Department of Pathology, Tennis Court Rd, Cambridge, UK.
Furlong
Robert A
RA
Conner
Sarah J
SJ
Kirkman-Brown
Jackson
J
Afnan
Masoud
M
Barratt
Christopher
C
Griffin
Darren K
DK
Affara
Nabeel A
NA
D053713:Azoospermia / Q000235:genetics; D001706:Biopsy; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D016207:Cytokines / Q000097:blood; D005091:Exons; D005786:Gene Expression Regulation; D006801:Humans; D007248:Infertility, Male / Q000235:genetics* / Q000473:pathology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D017471:Receptors, Interferon / Q000235:genetics; D027724:Reproductive Techniques, Assisted; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013081:Sperm Motility; D014158:Transcription, Genetic; D014649:Vas Deferens / Q000473:pathology; D014659:Vasectomy; D000096743:Interferon gamma Receptor
D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D016207:Cytokines; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor