Development of the fetal gubernaculum is a prerequisite for testicular descent and dependent upon insulin-like 3 and androgen, but knowledge of downstream effectors is limited. We analyzed transcript profiles in gubernaculum and testis to address changes occurring during normal and abnormal testicular descent in Long Evans wild type (wt) and cryptorchid (orl) fetuses. Total RNA from male wt and orl gubernacula (gestational days (GD) 18-20), wt female gubernacula (GD18) and testis (GD17 and 19) was hybridized to Affymetrix GeneChips. Statistical analysis of temporal, gender and strain-specific differences in gene expression was performed using linear models analysis with empirical Bayes statistics and ANOVA (gubernaculum) and linear analysis (testis). Over-represented common gene ontology functional categories and pathways were identified in groups of differentially expressed genes using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Transcript profiles were dynamic in wt males between GD18-19 and GD20, comparatively static in orl GD18-20 gubernaculum, and similar in wt and orl testis. Functional analysis of differentially expressed genes in wt and orl gubernaculum identified categories related to metabolism, cellular biogenesis, small GTPase-mediated signal transduction, cytoskeleton, muscle development and insulin signaling. Genes involved in androgen receptor signaling and/or regulated by androgens were over-represented in differentially expressed gubernaculum and testis gene groups. Quantitative RT-PCR confirmed differential expression of genes related to muscle development, including Myog, Tnnt2, Fst, Igf1, Igfbp5, Id2, and Msx1. These data suggest that the orl mutation results in a primary gubernacular defect that affects muscle development and cytoskeletal function and may alter androgen-regulated pathways.

Written by
Barthold JS, McCahan SM, Singh AV, Knudsen TB, Si X, Campion L, Akins RE.

Reference
J Androl. 2008 Jan 24. Epub ahead of print.
doi:10.2164/jandrol.107.003970

PubMed Abstract
PMID:18222913

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