Gene expression alterations in cryptorchid males using spermatozoal microarray analysis.
OBJECTIVE
To identify differential spermatozoal gene expression patterns using microarray between controls and patients with cryptorchidism.


METHODS
Prospective laboratory analysis.


METHODS
Pediatric urology clinic and laboratory of an academic hospital in the United States.


METHODS
Ten control patients and 12 cryptorchid males (8 unilateral, 4 bilateral).


METHODS
Ejaculates were collected and motile sperm were isolated by Percoll centrifugation, total RNA was extracted and verified using sperm-specific reverse transcriptase-polymerase chain reaction (RT-PCR). Biotin-labeled amplified RNA was hybridized to Affymetrix Human Genome Focus arrays. Differentially expressed genes were identified using permutation t-test.


METHODS
Semen analyses and differential spermatozoal gene expression patterns measured by microarray.


RESULTS
Mean semen volume was not different between control and patients with cryptorchidism. Mean sperm density was significantly decreased between control, unilateral, and bilateral cryptorchid samples (110 vs. 87 vs. 16 million/mL). From the microarray expression data, we identified 43 genes differentially expressed between the two groups. Thirty-eight genes were significantly underexpressed in the cryptorchid samples including many transcriptional factors (cul3, prm1, hspcd35) and a testis-specific cell-adhesion gene (tpx-1) involved in germ cell maturation and sperm tail formation. An antiapoptotic gene (TNFAIP3) was highly overexpressed in the cryptorchid samples.


CONCLUSIONS
Gene expression profiles offer insight into the diverse alterations that occur in cryptorchidism. The observed changes in spermatozoal expression of transcriptional and antiapoptotic genes may result in poor seminal parameters in formerly cryptorchid males.
Nguyen
Michael T
MT
Division of Urology, Children's Hospital of Philadelphia, 34th Street & Civic Center Blvd., Philadelphia, PA 19104, USA.
Delaney
Daniel P
DP
Kolon
Thomas F
TF
D000293:Adolescent; D000328:Adult; D001331:Automation; D051928:CD47 Antigen / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D015331:Cohort Studies; D003456:Cryptorchidism / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics; D004542:Ejaculation; D005784:Gene Amplification; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D008297:Male; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics; D012016:Reference Values; D012661:Semen / Q000502:physiology; D013081:Sperm Motility; D013094:Spermatozoa / Q000502:physiology*
D051928:CD47 Antigen; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D012313:RNA