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.

DESIGN

Prospective laboratory analysis.

SETTING

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

PATIENT(S): Ten control patients and 12 cryptorchid males (8 unilateral, 4 bilateral).

INTERVENTION(S): 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.

MAIN OUTCOME MEASURE(S): Semen analyses and differential spermatozoal gene expression patterns measured by microarray.

RESULT(S): 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.

CONCLUSION(S): 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.